PEDS Advance Access published online on March 21, 2007
Protein Engineering Design and Selection, doi:10.1093/protein/gzm008
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
REVIEW |
Design and application of stimulus-responsive peptide systems
1 Department of Chemical Engineering, Columbia University in the City of New York, 820 Mudd, MC4721, 500 W. 120th Street, New York, NY 10027, USA
2 To whom correspondence should be addressed. E-mail: sbanta{at}cheme.columbia.edu
 |
Abstract |
|---|
 Top Abstract IntroductionStimulus-responsive systems...Stimulus-responsive systems...Combinatorial methods for new...OutlookAcknowledgementsReferences |
|---|
The ability of peptides and proteins to change conformations in response to external stimuli such as temperature, pH and the presence of specific small molecules is ubiquitous in nature. Exploiting this phenomenon, numerous natural and designed peptides have been used to engineer stimulus-responsive systems with potential applications in important research areas such as biomaterials, nanodevices, biosensors, bioseparations, tissue engineering and drug delivery. This review describes prominent examples of both natural and designed synthetic stimulus-responsive peptide systems. While the future looks bright for stimulus-responsive systems based on natural and rationally engineered peptides, it is expected that the range of stimulants used to manipulate such systems will be significantly broadened through the use of combinatorial protein engineering approaches such as directed evolution. These new proteins and peptides will continue to be employed in exciting and high-impact research areas including bionanotechnology and synthetic biology.
Keywords: conformational changes/stimulus-responsive peptides/bionanotechnology
|
Introduction |
|---|
|
TopAbstractIntroductionStimulus-responsive systems...Stimulus-responsive systems...Combinatorial methods for new...OutlookAcknowledgementsReferences |
|---|
In nature, the action of proteins is frequently mediated by a significant conformational change. This conformational change is usually in response to environmental cues such as a change in pH, temperature or the binding of specific analytes. Researchers have been quick to exploit naturally available stimulus-responsive proteins or peptides to engineer stimulus-responsive systems with potential impact on various biotechnological applications, including biomaterials, nanodevices, biosensors, bioseparations, tissue engineering and drug delivery (Fig. 1). The connection between stimulus-responsive biomolecules in nature and systems engineered to respond to a stimulus is usually made by appropriately linking the natural stimulus-responsive molecule to the molecule mediating the function of interest. In addition to the use of natural stimulus-responsive peptides and proteins, novel peptide systems have also been created using rational protein design to undergo dramatic conformational changes in response to stimuli such as pH, temperature, light, redox state, physical forces or the presence of salts or metals. These rationally engineered stimulus-responsive peptide systems frequently involve stimulus-dependent self-assembly of the peptides to form larger macromolecular structures with potential utility in tissue engineering, drug delivery and biomaterials.
|
This review focuses on stimulus-responsive peptide systems, based on both naturally existing peptides and rationally engineered systems (Table I). The design of the stimulus-responsive systems and the value of the engineered systems in biotechnological applications are examined. Finally, the prospect of using combinatorial protein engineering approaches such as directed evolution for engineering stimulus-responsive peptide systems is discussed. The subject of engineering stimulus-responsive systems based on the insertion of entire protein domains that modulate the activity of another protein through a conformational change is not covered by this review, and interested readers are referred to a previous review published in this journal (Ostermeier, 2005
). Readers interested in stimulus-responsive synthetic polymeric systems for biochemical applications are referred to elsewhere (Roy and Gupta, 2003).
|
|
Stimulus-responsive systems based on existing proteins |
|---|
|
TopAbstractIntroductionStimulus-responsive systems...Stimulus-responsive systems...Combinatorial methods for new...OutlookAcknowledgementsReferences |
|---|
Through the careful study of the structures and functions of natural proteins, several peptide motifs have been identified that exhibit environmentally responsive structural behavior. Several of these peptides have been fused to other proteins, in order to make them more attractive for use in biotechnological applications (Table I). The most widely used of the stimulus-responsive natural peptides is the repeating pentameric sequence VPGVG, found in the polymeric elastin-like polypeptide (ELP) of the mammalian elastin protein. The fourth residue of this pentamer, the ‘guest residue’, can be varied to any amino acid except proline to alter the physicochemical properties of the ELP (Meyer and Chilkoti, 2004
). When used in a highly multimeric form (20–300 pentameric repeats), the resulting ELP exhibits a sharp reversible hydrophilic–hydrophobic phase transition that is triggered by changes in temperature, pH or ionic strength. The temperature at which this transition occurs is termed the transition temperature, Tt. At temperatures below Tt, the ELP exists in an extended state and is soluble in water, while at temperatures above Tt, the ELP collapses into an ordered ß-spiral that aggregates and precipitates out of solution.
Much of our knowledge about the pentameric elastin sequence and ELPs stems from studies carried out by Dan Urry. These studies include, but are not limited to, characterization of the effect of the nature and length of ELP sequences on the transition temperature, as well as analysis of the physical properties of ELPs (for examples, see Urry et al., 1985, 1986, 1991, 1992). Other studies have also shed light on the relationship between the sequence or length of ELPs with the transition temperature (Reiersen et al., 1998; Meyer and Chilkoti, 2004).
The inverse transition temperature of ELPs has prompted the creation of synthetic ELPs that, when fused to a protein or peptide of interest, enable the reversible temperature-dependent switching of the biotechnologically useful behavior (Table I). For example, the temperature-responsive phase transition of ELPs has been exploited to develop numerous systems for purification of biomolecules. Fusion of ELPs to a protein followed by a temperature-induced precipitation process, termed as inverse transition cycling, was used to purify numerous recombinantly expressed proteins (Meyer and Chilkoti, 1999, 2004; Chilkoti et al., 2002; Hyun et al., 2004; McHale et al., 2005; Chow et al., 2006; Furgeson et al., 2006). Fusion of both an ELP and a self-cleavable intein has been used to purify 10 different proteins based on temperature-induced precipitation without the introduction of extraneous tags in the final purified product (Banki et al., 2005). A temperature-responsive purification of plasmid DNA has also been enabled by fusion of ELPs to a DNA-binding protein (Kostal et al., 2004).
In addition to purification applications, the stimulus-responsive properties of ELPs fused to appropriate peptides or proteins have been used for remediation of toxic metals (Kostal et al., 2003; Prabhukumar et al., 2004) and targeted drug delivery. For the latter application, thermally responsive drug delivery was achieved either through selective aggregation of drugs (Meyer et al., 2001; Raucher and Chilkoti, 2001; Furgeson et al., 2006) or through thermal activation of drug-bearing cell penetrating peptides (Bidwell and Raucher, 2005; Massodi et al., 2005), in hyperthermic solid tumors.
A single copy or small number (2–3) of copies of the elastin pentameric repeat sequence VPGXG has been used to modulate the functionality of proteins. Introduction of the sequence GVPGVG into the inter-helix region of an IgG-binding two-helix region of staphylococcal protein A allowed an increased 
-helical structure and strengthened binding to Fc with increasing temperature (Reiersen and Rees, 1999). A similar system also permitted salt-dependent binding of an elastin peptide-containing IgG minidomain to the Fc target (Reiersen and Rees, 2000). In another study, incorporation of 1–3 copies of the VPGXG sequence into the linker region of anti-fluorescein single-chain antibodies enabled destabilization of the scFv leading to unbinding of the scFv from fluorescein at increased temperatures (Megeed et al., 2006).
Another stimulus-responsive system inspired by a natural peptide is a calcium-switchable mesh with potential for application as a smart biomaterial (Ringler and Schulz, 2003). This system utilizes repeats of the characteristic calcium-binding motif GGXGXDXUX from the ß-roll domain of the enzyme serralysin from Serratia marcescens (Baumann, 1994), where X is any amino acid and U is a large aliphatic residue. A calcium-responsive hydrogel for application in tissue engineering has also been created from the larger calcium-binding protein, calmodulin (Ehrick et al., 2005).
Other natural stimulus-responsive peptides that have yet to find their way to practical applications also exist (Table I). A 36-amino acid peptide of the influenza virus protein hemagglutinin, important for membrane fusion of the virus, has been synthesized and was shown to exhibit an increased -helical content at low pH (Carr and Kim, 1993). This peptide has potential for application in molecular motors and machines (Dubey et al., 2004; Mavroidis et al., 2004; Banta et al., 2007). Other environmentally sensitive molecules include a 25-residue peptide from a sheep prion protein whose conformation is dependent on the hydrophobicity of the solvent (Megy et al., 2004), and a 31-amino acid peptide from a marsupial prion protein, whose conformation can be modulated by divalent copper ions (Gustiananda et al., 2002).
|
Stimulus-responsive systems based on rational design |
|---|
|
TopAbstractIntroductionStimulus-responsive systems...Stimulus-responsive systems...Combinatorial methods for new...OutlookAcknowledgementsReferences |
|---|
Several peptide-based systems have rationally been engineered, both de novo and as modifications to existing proteins, to respond in interesting ways to various stimuli (Table I). Many of these systems are tunable via changes in temperature and/or pH. For example, an early study described the de novo creation of bis-amphiphilic peptides that switched states from an
-helix to a ß-sheet in aqueous solution in a pH-dependent manner (Mutter et al., 1991). Peptides inspired by segments of the native proteins IsK and hen egg white lysozyme that self-assemble into gels comprising ß-sheet tapes were found to dissociate at pH > 12 (Aggeli et al., 1997). In work aimed at elucidating the formation of amyloid fibrils involved in numerous human diseases, certain 12- and 16-residue peptides with alternating hydrophobic and charged amino acids were found to exhibit a conformational change from a self-assembled ß-sheet formation to an -helical structure at temperatures >70°C (Fig. 2) (Zhang and Rich, 1997; Altman et al., 2000). With cooling, these peptides retained the -helix structure, and took several weeks at room temperature to partially return to the ß-sheet form. These peptides were also found to reversibly undergo significant conformational changes dependent on pH. In analogous work, again aimed at amyloid study, a rationally designed 17-residue peptide with both -helical and ß-type elements was found to irreversibly change states from a coiled-coil to a ß-sheet at elevated temperatures (Kammerer et al., 2004), and a 29-residue peptide designed to have both -helical- and ß-sheet-like properties displayed a reversible heat-induced conversion from an -helix to ß-sheet form (Ciani et al., 2002). Responsive 20-residue peptides have also been designed de novo with alternating hydrophobic and hydrophilic residues and a central type II' turn structure in order to reversibly fold from a disordered state to a ß-hairpin structure. This conformational shift, which leads to the formation of a hydrogel, was made responsive both to changes in pH (Schneider et al., 2002) and temperature (Pochan et al., 2003) by appropriately tailoring the peptide primary sequence. Variation of the solution pH has also been used to trigger the reversible assembly of a synthetic polymer-peptide amphiphile into nanotubes (Hartgerink et al., 2001), and reversibly direct a 21-residue peptide to form a mechanically strong ‘film state’ (at neutral pH) versus a mobile ‘detergent state’ (at acidic pH) at a fluid–fluid interface (Dexter et al., 2006).
|
Agents that enhance the hydrophobic effect such as salts have been used to alter the microenvironment surrounding peptides and thus trigger peptide aggregation (Table I). This has been achieved either through the design of ionic self-complementary peptides containing alternating hydrophobic and charged amino acids that assemble into macromolecular structures such as hydrogels and membranes upon salt exposure (Zhang et al., 1993
; Holmes et al., 2000), or peptides that salt-dependently associate with ‘sticky-ends’, promoting self-assembly into fibers and filaments (Wagner et al., 2005). Interestingly, a ‘sticky-ended’ peptide assembly system reliant on ionic rather than hydrophobic interactions is inhibited, not enhanced, by the presence of salt (Pandya et al., 2000).
Peptides have also been designed to change their conformation in response to redox state (Dado and Gellman, 1993; Pandya et al., 2004), and the -helical content of a peptide chemically modified with an azobenzene derivative was found to be reversibly controllable by light (Kumita et al., 2000). Peptides whose bulk behavior can be controlled by divalent metal ions (Cerasoli et al., 2005; Dexter et al., 2006) and an externally applied physical trigger, shear (Aggeli et al., 1997), have also been successfully engineered. In other interesting work, 15-residue peptides N-terminally modified with pyridyl functionalities were created with the ability to self-assemble into a triple-helix metalloprotein in response to Ni2+, Co2+ or Ru(II) metals (Ghadiri et al., 1992a), or a four-helix metalloprotein in response to Ru(II) (Ghadiri et al., 1992b).
An emerging area of interest in the field of stimulus-responsive peptides is the concept of enzyme-responsive peptides. For example, hydrophobic dipeptides in combination with Fmoc-modified amino acids were found to self-assemble to form hydrogels under appropriate conditions, in the presence of the protease thermolysin (Toledano et al., 2006). Peptides cleavable by specific proteases offer the potential to create smart hydrogels that can be programmed to change their properties upon protease exposure (Thornton et al., 2005; Zourob et al., 2006).
Many designed responsive peptides that self-assemble into interesting macromolecular structures have been formulated to solve important biological problems. With an eye toward application as a scaffold for tissue engineering, ionic self-complementary peptides that salt dependently self-assemble into a macromolecular membranous matrix have been used to support the attachment of various mammalian cells (Zhang et al., 1995), including the attachment of neuronal cells, enabling extensive neurite outgrowth (Holmes et al., 2000). Peptide amphiphiles that self-assemble into nanotubes at low pHs were able to direct mineralization of hydroxyapatite in a process that mimics natural bone formation (Hartgerink et al., 2001). Polypeptide-based diblock copolymers that self-assemble into vesicles and micelles whose stability and/or size can be controlled by pH or ionic strength have been proposed as smart, tunable alternatives to conventional lipid vesicles for drug delivery applications. Vesicles whose integrity can be manipulated by changes in pH have been constructed by linking together diblock copolypeptides comprising a hydrophobic poly-L-leucine chain and hydrophilic ethylene glycol-modified poly-L-lysine chain (Bellomo et al., 2004). These vesicles were made pH-sensitive by spiking lysine residues, whose protonation state can affect chain conformation, into the hydrophobic poly-leucine block. Hybrid polypeptide-synthetic polymer diblock vesicles whose size is pH- and ionic strength-sensitive were constructed with a polybutadiene hydrophobic block and a poly-L-glutamic acid hydrophilic block (Checot et al., 2005). Other self-assembling peptide systems have the potential to be used as biomaterials such as fibers, filaments, nano-ropes, nano-tapes and membranes, in addition to hydrogels for tissue engineering (Zhang et al., 1993; Aggeli et al., 1997; Pandya et al., 2000; Wagner et al., 2005). Peptides that self-assemble on surfaces can serve to reinforce surfaces or infuse the surface with new functionality (Ryadnov et al., 2003; Lu et al., 2004; Dexter et al., 2006).
|
Combinatorial methods for new stimulus-responsive systems |
|---|
|
TopAbstractIntroductionStimulus-responsive systems...Stimulus-responsive systems...Combinatorial methods for new...OutlookAcknowledgementsReferences |
|---|
Natural and rationally engineered peptides will continue to see use in important and diverse biotechnology applications. However, the currently available stimuli-responsive peptides may be limited by the scope and breadth of available environmental cues that can induce peptide conformational changes. Until our understanding of peptide structure–function relationships fully enables de novo design, engineering of novel stimulus-responsive peptide systems that populate two or more distinct equilibrium states will likely be greatly facilitated by the utilization of combinatorial methods.
Directed evolution is a combinatorial method that utilizes a selection or screening procedure to identify proteins or peptides with desired properties from randomized libraries (Kuchner and Arnold, 1997). A significant advantage of the directed evolution approach is that a priori knowledge of a protein's structure–function relationship is not required. The main technical challenge in directed evolution is the development of appropriate selection or screening techniques (Zhao and Arnold, 1997). This is particularly true for the directed evolution of stimulus-responsive peptides, as the determination of the onset of a conformational change in a peptide is not a readily observable event.
To attempt to overcome this barrier, we are developing protein-based conformational change sensors (CCSs). These sensors can then be used for the directed evolution of novel stimulus-responsive peptides. As a first proof of this principle, we are developing a sensor starting with an anti-fluorescein single chain antibody construct (scFv) (Jung and Pluckthun, 1997). It is well known that the properties of the artificial peptide linkers that tether the VL and VH domains together in the scFv format can dramatically affect the performance of the scFv (Tang et al., 1996). Therefore, the binding properties of the scFv can be used to report the conformational state of the linker. This effect has recently been demonstrated when temperature-responsive fluorescein binding was observed following the insertion of a short elastin-like peptide into the scFv linker (Fig. 3) (Megeed et al., 2006).
|
The selection of randomized peptide libraries inserted into the scFv construct for unique conformational behaviors is being performed in our laboratory using an immobilized fluorescein affinity column. This allows for the quantitative prediction of scFv binding affinities based on measured elution times using affinity chromatography models, and this prediction is being used to infer information about the conformational state of the inserted peptide linkers. Since peptides with novel stimulus responsiveness are desired, a dual positive–negative selection approach is needed. For the negative selection, peptides that have a conformation that enables fluorescein binding are recovered. For the positive selection, the desired stimulus is introduced and scFvs that exhibit weakened binding affinities in response to the stimulus of interest are eluted.
To the best of our knowledge, this will be the first demonstration of directed evolution for stimulus-responsive peptide conformational changes. Additional CCSs will be developed, which are calibrated to enable the identification of other peptides that exhibit novel triggered conformational behaviors. These methods will provide a new tool for engineering novel stimulus-responsive peptide systems for use in the various applications described in this paper.
|
Outlook |
|---|
|
TopAbstractIntroductionStimulus-responsive systems...Stimulus-responsive systems...Combinatorial methods for new...OutlookAcknowledgementsReferences |
|---|
As our understanding of protein structures and functions continues to expand, researchers are increasingly using proteins and peptides to create new systems that have no natural counterparts. Modular assembly concepts are being used to create proteins and protein-based systems that have structural applications in addition to the chemical capabilities for which proteins are often associated. As fields such as synthetic biology and bionanotechnology continue to mature, an ever-increasing toolbox of parts will be needed for the creation of future technological advances.
Stimulus-responsive peptides will be valuable building blocks as systems are created that can respond to environmental cues. This technology can be used to make ‘smart’ systems, including artificial viruses, tunable tissue culture scaffolds and other bionanomachines. Rational protein design will continue to be used to create new peptides, and directed evolution will likely be used to further broaden these exciting efforts.
|
Footnotes |
|---|
Edited by Dan Tawzik
|
Acknowledgements |
|---|
|
TopAbstractIntroductionStimulus-responsive systems...Stimulus-responsive systems...Combinatorial methods for new...OutlookAcknowledgementsReferences |
|---|
This work was funded in part by a James D. Watson Investigator Award to S.B. from the New York State Office of Science, Technology, and Academic Research (NYSTAR).
|
References |
|---|
|
TopAbstractIntroductionStimulus-responsive systems...Stimulus-responsive systems...Combinatorial methods for new...OutlookAcknowledgementsReferences |
|---|
Aggeli A., Bell M., Boden N., Keen J.N., Knowles P.F., McLeish T.C., Pitkeathly M., Radford S.E. (1997) Nature 386:259–262.[CrossRef][Medline]
Aggeli A., Bell M., Carrick L.M., Fishwick C.W., Harding R., Mawer P.J., Radford S.E., Strong A.E., Boden N. (2003) J. Am. Chem. Soc. 125:9619–9628.[CrossRef][Web of Science][Medline]
Altman M., Lee P., Rich A., Zhang S. (2000) Protein Sci. 9:1095–1105.[Web of Science][Medline]
Banki M.R., Feng L., Wood D.W. (2005) Nat. Methods 2:659–661.[CrossRef][Web of Science][Medline]
Banta S., Megeed Z., Casali M., Rege K., Yarmush M.L. (2007) J. Nanosci. Nanotechnol. 7:387–401.
Baumann U. (1994) J. Mol. Biol. 242:244–251.[CrossRef][Web of Science][Medline]
Bellomo E.G., Wyrsta M.D., Pakstis L., Pochan D.J., Deming T.J. (2004) Nat. Mater. 3:244–248.[CrossRef][Web of Science][Medline]
Bidwell G.L. III. and Raucher D. (2005) Mol. Cancer Ther. 4:1076–1085.
Caplan M.R., Moore P.N., Zhang S., Kamm R.D., Lauffenburger D.A. (2000) Biomacromolecules 1:627–631.[CrossRef][Web of Science][Medline]
Caplan M.R., Schwartzfarb E.M., Zhang S., Kamm R.D., Lauffenburger D.A. (2002) Biomaterials 23:219–227.[CrossRef][Web of Science][Medline]
Carr C.M. and Kim P.S. (1993) Cell 73:823–832.[CrossRef][Web of Science][Medline]
Cerasoli E., Sharpe B.K., Woolfson D.N. (2005) J. Am. Chem. Soc. 127:15008–15009.[CrossRef][Web of Science][Medline]
Cerpa R., Cohen F.E., Kuntz I.D. (1996) Fold Des. 1:91–101.[CrossRef][Web of Science][Medline]
Checot F., Brulet A., Oberdisse J., Gnanou Y., Mondain-Monval O., Lecommandoux S. (2005) Langmuir 21:4308–4315.[CrossRef][Web of Science][Medline]
Chilkoti A., Dreher M.R., Meyer D.E., Raucher D. (2002) Adv. Drug. Deliv. Rev. 54:613–630.[CrossRef][Web of Science][Medline]
Chow D.C., Dreher M.R., Trabbic-Carlson K., Chilkoti A. (2006) Biotechnol. Prog. 22:638–646.[CrossRef][Medline]
Ciani B., Hutchinson E.G., Sessions R.B., Woolfson D.N. (2002) J. Biol. Chem. 277:10150–10155.
Collier J.H. and Messersmith P.B. (2003) Bioconjug. Chem. 14:748–755.[CrossRef][Web of Science][Medline]
Collier J.H. and Messersmith P.B. (2004) Adv. Mater. 16:907–910.
Collier J.H., Hu B.H., Ruberti J.W., Zhang J., Shum P., Thompson D.H., Messersmith P.B. (2001) J. Am. Chem. Soc. 123:9463–9464.[CrossRef][Web of Science][Medline]
Dado G.P. and Gellman S.H. (1993) J. Am. Chem. Soc. 115:12609–12610.
Davis M.E., Motion J.P., Narmoneva D.A., Takahashi T., Hakuno D., Kamm R.D., Zhang S., Lee R.T. (2005) Circulation 111:442–450.
Dexter A.F., Malcolm A.S., Middelberg A.P. (2006) Nat. Mater. 5:502–506.[CrossRef][Web of Science][Medline]
Dong H. and Hartgerink J.D. (2006) Biomacromolecules 7:691–695.[CrossRef][Web of Science][Medline]
Dubey A.G., Sharma C., Mavroidis S.M., Tomassone S.M., Nickitczuk K.P., Yarmush M.L. (2004) J. Comput. Theor. Nanosci. 1:18–28.
Dutta K., Alexandrov A., Huang H., Pascal S.M. (2001) Protein Sci. 10:2531–2540.[CrossRef][Web of Science][Medline]
Dutta K., Engler F.A., Cotton L., Alexandrov A., Bedi G.S., Colquhoun J., Pascal S.M. (2003) Protein Sci. 12:257–265.[CrossRef][Web of Science][Medline]
Ehrick J.D., Deo S.K., Browning T.W., Bachas L.G., Madou M.J., Daunert S. (2005) Nat. Mater. 4:298–302.[Web of Science][Medline]
Ellis-Behnke R.G., Liang Y.X., You S.W., Tay D.K., Zhang S., So K.F., Schneider G.E. (2006) Proc. Natl Acad. Sci. USA 103:5054–5059.
Furgeson D.Y., Dreher M.R., Chilkoti A. (2006) J. Control Release. 110:362–369.[CrossRef][Web of Science][Medline]
Ghadiri M.R., Soares C., Choi C. (1992a) J. Am. Chem. Soc. 114:825–831.
Ghadiri M.R., Soares C., Choi C. (1992b) J. Am. Chem. Soc. 114:4000–4002.
Gustiananda M., Haris P.I., Milburn P.J., Gready J.E. (2002) FEBS Lett. 512:38–42.[CrossRef][Web of Science][Medline]
Hartgerink J.D., Beniash E., Stupp S.I. (2001) Science 294:1684–1688.
Holmes T.C., de Lacalle S., Su X., Liu G., Rich A., Zhang S. (2000) Proc. Natl Acad. Sci. USA 97:6728–6733.
Hyun J., Lee W.K., Nath N., Chilkoti A., Zauscher S. (2004) J. Am. Chem. Soc. 126:7330–7335.[CrossRef][Web of Science][Medline]
Jung S. and Pluckthun A. (1997) Protein Eng. 10:959–966.
Kammerer R.A., Kostrewa D., Zurdo J., Detken A., Garcia-Echeverria C., Green J.D., Muller S.A., Meier B.H., Winkler F.K., Dobson C.M., Steinmetz M.O. (2004) Proc. Natl Acad. Sci. USA 101:4435–4440.
Kayser V., Turton D.A., Aggeli A., Beevers A., Reid G.D., Beddard G.S. (2004) J. Am. Chem. Soc. 126:336–343.[Web of Science][Medline]
Kisiday J., Jin M., Kurz B., Hung H., Semino C., Zhang S., Grodzinsky A.J. (2002) Proc. Natl Acad. Sci. USA 99:9996–10001.
Kostal J., Mulchandani A., Gropp K.E., Chen W. (2003) Environ. Sci. Technol. 37:4457–4462.[Medline]
Kostal J., Mulchandani A., Chen W. (2004) Biotechnol. Bioeng. 85:293–297.[CrossRef][Web of Science][Medline]
Kovaric B.C., Kokona B., Schwab A.D., Twomey M.A., de Paula J.C., Fairman R. (2006) J. Am. Chem. Soc. 128:4166–4167.[CrossRef][Web of Science][Medline]
Kretsinger J.K., Haines L.A., Ozbas B., Pochan D.J., Schneider J.P. (2005) Biomaterials 26:5177–5186.[CrossRef][Web of Science][Medline]
Kuchner O. and Arnold F.H. (1997) Trends Biotechnol. 15:523–530.[CrossRef][Web of Science][Medline]
Kumita J.R., Smart O.S., Woolley G.A. (2000) Proc. Natl Acad. Sci. USA 97:3803–3808.
Lu J.R., Perumal S., Hopkinson I., Webster J.R., Penfold J., Hwang W., Zhang S. (2004) J. Am. Chem. Soc. 126:8940–8947.[CrossRef][Web of Science][Medline]
Massodi I., Bidwell G.L. III., Raucher D. (2005) J. Control Release 108:396–408.[CrossRef][Web of Science][Medline]
Mavroidis C., Dubey A., Yarmush M.L. (2004) Annu. Rev. Biomed. Eng. 6:363–395.[CrossRef][Web of Science][Medline]
McHale M.K., Setton L.A., Chilkoti A. (2005) Tissue Eng. 11:1768–1779.[CrossRef][Web of Science][Medline]
Megeed Z., Winters R.M., Yarmush M.L. (2006) Biomacromolecules 7:999–1004.[CrossRef][Web of Science][Medline]
Megy S., Bertho G., Kozin S.A., Debey P., Hoa G.H., Girault J.P. (2004) Protein Sci. 13:3151–3160.[CrossRef][Web of Science][Medline]
Meyer D.E. and Chilkoti A. (1999) Nat. Biotechnol. 17:1112–1115.[CrossRef][Web of Science][Medline]
Meyer D.E. and Chilkoti A. (2004) Biomacromolecules 5:846–851.[CrossRef][Web of Science][Medline]
Meyer D.E., Kong G.A., Dewhirst M.W., Zalutsky M.R., Chilkoti A. (2001) Cancer Res. 61:1548–1554.
Mutter M. and Hersperger R. (1990) Angew. Chem. Int. Ed. Engl. 29:185–187.
Mutter M., Gassmann R., Buttkus U., Altmann K.H. (1991) Angew. Chem. Int. Ed. Engl. 30:1514–1516.
Narmoneva D.A., Oni O., Sieminski A.L., Zhang S., Gertler J.P., Kamm R.D., Lee R.T. (2005) Biomaterials 26:4837–4846.[CrossRef][Web of Science][Medline]
Ostermeier M. (2005) Protein Eng. Des. Sel. 18:359–364.
Pandya M.J., Spooner G.M., Sunde M., Thorpe J.R., Rodger A., Woolfson D.N. (2000) Biochemistry 39:8728–8734.[CrossRef][Medline]
Pandya M.J., Cerasoli E., Joseph A., Stoneman R.G., Waite E., Woolfson D.N. (2004) J. Am. Chem. Soc. 126:17016–17024.[CrossRef][Web of Science][Medline]
Pochan D.J., Schneider J.P., Kretsinger J., Ozbas B., Rajagopal K., Haines L. (2003) J. Am. Chem. Soc. 125:11802–11803.[CrossRef][Web of Science][Medline]
Prabhukumar G., Matsumoto M., Mulchandani A., Chen W. (2004) Environ. Sci. Technol. 38:3148–3152.
Raghuraman H. and Chattopadhyay A. (2006) Biopolymers 83:111–121.[CrossRef][Web of Science][Medline]
Raucher D. and Chilkoti A. (2001) Cancer Res. 61:7163–7170.
Reches M. and Gazit E. (2003) Science 300:625–627.
Reiersen H., Clarke A.R., Rees A.R. (1998) J. Mol. Biol. 283:255–264.[CrossRef][Web of Science][Medline]
Reiersen H. and Rees A.R. (1999) Biochemistry 38:14897–14905.[CrossRef][Medline]
Reiersen H. and Rees A.R. (2000) Biochem. Biophys. Res. Commun. 276:899–904.[CrossRef][Web of Science][Medline]
Ringler P. and Schulz G.E. (2003) Science 302:106–109.
Roy I. and Gupta M.N. (2003) Chem. Biol. 10:1161–1171.[CrossRef][Web of Science][Medline]
Ryadnov M.G., Ceyhan B., Niemeyer C.M., Woolfson D.N. (2003) J. Am. Chem. Soc. 125:9388–9394.[CrossRef][Web of Science][Medline]
Schneider J.P., Pochan D.J., Ozbas B., Rajagopal K., Pakstis L., Kretsinger J. (2002) J. Am. Chem. Soc. 124:15030–15037.[CrossRef][Web of Science][Medline]
Schuh M.D. and Baldwin M.C. (2006) J. Phys. Chem. B Condens. Matter Mater. Surf. Interfaces Biophys. 110:10903–10909.[Medline]
Tang Y., Jiang N., Parakh C., Hilvert D. (1996) J. Biol. Chem. 271:15682–15686.
Thornton P.D., McConnell G., Ulijn R.V. (2005) Chem. Commun. (Camb) 5913–5915.
Toledano S., Williams R.J., Jayawarna V., Ulijn R.V. (2006) J. Am. Chem. Soc. 128:1070–1071.[CrossRef][Web of Science][Medline]
Urry D.W., Trapane T.L., Prasad K.U. (1985) Biopolymers 24:2345–2356.[CrossRef][Web of Science][Medline]
Urry D.W., Haynes B., Harris R.D. (1986) Biochem. Biophys. Res. Commun. 141:749–755.[CrossRef][Web of Science][Medline]
Urry D.W., Luan C.H., Parker T.M., Gowda D.C., Prasad K.U., Reid M.C., Safavy A. (1991) J. Am. Chem. Soc. 113:4346–4348.
Urry D.W., Gowda D.C., Parker T.M., Luan C.H., Reid M.C., Harris C.M., Pattanaik A., Harris R.D. (1992) Biopolymers 32:1243–1250.[CrossRef][Web of Science][Medline]
Wagner D.E., Phillips C.L., Ali W.M., Nybakken G.E., Crawford E.D., Schwab A.D., Smith W.F., Fairman R. (2005) Proc. Natl Acad. Sci. USA 102:12656–12661.
Waterhous D.V. and Johnson W.C. Jr. (1994) Biochemistry 33:2121–2128.[CrossRef][Medline]
Yokoi H., Kinoshita T., Zhang S. (2005) Proc. Natl Acad. Sci. USA 102:8414–8419.
Zhang S. (2002) Biotechnol. Adv. 20:321–339.[CrossRef][Web of Science][Medline]
Zhang S. and Rich A. (1997) Proc. Natl Acad. Sci. USA 94:23–28.
Zhang S., Holmes T., Lockshin C., Rich A. (1993) Proc. Natl Acad. Sci. USA 90:3334–3338.
Zhang S., Holmes T.C., DiPersio C.M., Hynes R.O., Su X., Rich A. (1995) Biomaterials 16:1385–1393.[CrossRef][Web of Science][Medline]
Zhao H. and Arnold F.H. (1997) Curr. Opin. Struct. Biol. 7:480–485.[CrossRef][Web of Science][Medline]
Zhong L. and Johnson W.C. Jr. (1992) Proc. Natl Acad. Sci. USA 89:4462–4465.
Zimenkov Y., Dublin S.N., Ni R., Tu R.S., Breedveld V., Apkarian R.P., Conticello V.P. (2006) J. Am. Chem. Soc. 128:6770–6771.[CrossRef][Web of Science][Medline]
Zirah S., Kozin S.A., Mazur A.K., Blond A., Cheminant M., Segalas-Milazzo I., Debey P., Rebuffat S. (2006) J. Biol. Chem. 281:2151–2161.
Zourob M., Gough J.E., Ulijn R.V. (2006) Adv. Mater. 18:655–659.
Received December 4, 2006; revised January 10, 2007; accepted January 18, 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  I. R. Wheeldon, J. W. Gallaway, S. C. Barton, and S. Banta Bioelectrocatalytic hydrogels from electron-conducting metallopolypeptides coassembled with bifunctional enzymatic building blocks PNAS, October 7, 2008; 105(40): 15275 - 15280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Casali, S. Banta, C. Zambonelli, Z. Megeed, and M. L. Yarmush Site-directed mutagenesis of the hinge peptide from the hemagglutinin protein: enhancement of the pH-responsive conformational change Protein Eng. Des. Sel., June 1, 2008; 21(6): 395 - 404. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||