In general, proteins fold with hydrophobic residues buried, away from water. Reversible protein folding due to hydrophobic interactions results from inverse temperature transitions where folding occurs on raising the temperature. Because homoiothermic animals constitute an infinite heat reservoir, it is the transition temperature, Tt, not the endothermic heat of the transition, that determines the hydrophobically folded state of polypeptides at body temperature. Reported here is a new hydrophobicity scale based on the values of Tt for each amino acid residue as a guest in a natural repeating peptide sequence, the high polymers of which exhibit reversible inverse temperature transitions. Significantly, a number of ways have been demonstrated for changing Tt such that reversibly lowering Tt from above to below physiological temperature becomes a means of isothermally and reversibly driving hydrophobic folding. Accordingly, controlling Tt becomes a mechanism whereby proteins can be induced to carry out isothermal free energy transduction.

No abstract

During the last half century, identification of an ideal (predominantly entropic) protein elastomer was generally thought to require that the ideal protein elastomer be a random chain network. Here, we report two new sets of data and review previous data. The first set of new data utilizes atomic force microscopy to report single-chain force-extension curves for (GVGVP) 251 and (GVGIP) 260 , and provides evidence for single-chain ideal elasticity. The second class of new data provides a direct contrast between lowfrequency sound absorption (0.1-10 kHz) exhibited by random-chain network elastomers and by elastin protein-based polymers.Earlier composition, dielectric relaxation (1-1000 MHz), thermoelasticity, molecular mechanics and dynamics calculations and thermodynamic and statistical mechanical analyses are presented, that combine with the new data to contrast with random-chain network rubbers and to detail the presence of regular non-random structural elements of the elastin-based systems that lose entropic elastomeric force upon thermal denaturation.The data and analyses affirm an earlier contrary argument that components of elastin, the elastic protein of the mammalian elastic fibre, and purified elastin fibre itself contain dynamic, non-random, regularly repeating structures that exhibit dominantly entropic elasticity by means of a damping of internal chain dynamics on extension.

The complete series of the recommended generic biological tests for materials and devices in contact with tissues and tissue fluids and blood have been carried out by an independent testing laboratory on the elastic protein-based (bioelastic) polymer, Poly(L-Val1-L-Pro2-Gly3-L-Val 4-Gly5) with a degree of polymerization greater than 120, and its 20 Mrad γ-irradiation cross linked elastic matrix, X20-poly(VPGVG). The specific tests and the summarized results given in parentheses are: (1) the Ames mutagenicity test (non- mutagenic), (2) cytotoxicity-agarose overlay (non-toxic), (3) acute systemic tox icity (non-toxic), (4) intracutaneous toxicity (non-toxic), (5) muscle implantation (favorable), (6) acute intraperitoneal toxicity (non-toxic), (7) systemic antigenic ity (non-antigenic), (8) dermal sensitization—the Magnusson and Kligman maximization method (non-sensitizing), (9) pyrogenicity (non-pyrogenic), (10) Lee White clotting study (normal clotting time), and (11) in vitro hemolysis test (non-hemolytic). Thus, this new elastomeric polypeptide biomaterial which is based on the most striking repeating sequence in the mammalian elastic fiber exhibits an extraordinary biocompatibility. This parent bioelastic material and a wide range of component peptide variations are under development for an equally wide range of potential medical applications such as prevention of adhesions, drug delivery, and synthetic arteries.

TMDSC data have been employed to observe the effect of NaCl on the inverse temperature transition of the model elastin-like polymer (GVGVP)251. NaCl causes a decrease in Tt and an increase in DeltaH. The increase in enthalpy appears both in the enthalpy related with the folding of the polymer and in the contribution associated with disruption of the structured water of hydrophobic hydration. It has been suggested that the presence of NaCl may cause a better formation of water structures surrounding the apolar polymer chains.