Peptides, extended arrangements

Extended Arrangements of Peptides and Proteins. Amino acids are finked from the carboxyl to the amine with formation of an amide bond, often referred to as the peptide fink. The repeating (— N—C — CO—) unit is called the peptide or protein backbone. Peptides and proteins differ only in the number of amino acids present in the biopolymer chain. The cutoff is arbitrarily set. Often, but not always, a peptide is designated as having fewer than 100 amino acids and the protein possesses more. Backbone amide groups have been found to play a role in enzyme catalysis. 

To prevent insolubility resulting from uncontrolled aggregation of extended strands, two adjacent parallel or antiparallel yS-peptide strands can be connected with an appropriate turn segment to form a hairpin. The / -hairpin motif is a functionally important secondary structural element in proteins which has also been used extensively to form stable and soluble a-peptide y9-sheet arrangements in model systems (for reviews, see [1, 4, 5] and references therein). The need for stable turns that can bring the peptide strands into a defined orientation is thus a prerequisite for hairpin formation. For example, type F or II" turns formed by D-Pro-Gly and Asn-Gly dipeptide sequences have been found to promote tight a-pep-tide hairpin folding in aqueous solution. Similarly, various connectors have been... 

While conformation II (Fig. 2.34) of Uke-y -amino acids is found in the 2.614-helical structure, conformation I, which similarly does not suffer from sy -pen-tane interaction, should be an appropriate alternative for the construction of sheet-like structures. However, sheet-like arrangement have not been reported so far for y-peptides composed of acyclic y " -amino acid residues. Nevertheless, other conformational biases (such as a,/9-unsaturation, cyclization between C(a) and C(y)) have been introduced into the y-amino acid backbone to restrict rotation around ethylene bonds and to promote extended conformation with formation of sheets in model peptides. Examples of such short chain y-peptides forming antiparallel (e.g. 152 [208]) and parallel (e.g. 153-155 [205, 208]) sheet-hke structures are shown in Fig. 2.38. 

Figure 11.2 The secondary structure of proteins. The simplest spatial arrangement of amino acids in a polypeptide chain is as a fully extended chain (a) which has a regular backbone structure due to the bond angles involved and from which the additional atoms, H and O, and the amino acid residues, R, project at varying angles. The helical form (b) is stabilized by hydrogen bonds between the —NH group of one peptide bond and the —CO group of another peptide bond. The amino acid residues project from the helix rather than internally into the helix.

The most stable elements of secondary structure of peptides and proteins are turns, helices, and extended conformations. Within each of these 3D-structures the most commonly found representatives are (3-turns,a-helices, and antiparallel (3-sheet conformations, respectively. y-TurnsJ5 310-helices, poly(Pro) helices, and (3-sheet conformations with a parallel strand arrangement have also been observed, although less frequently. Among the many types of (3-turns classified, type-I, type-II, and type-VI are the most usual, all being stabilized by an intramolecular i <— i+3 (backbone)C=0 -H—N(backbone) H-bond and characterized by either a tram (type-I and type-II) or a cis (type-VI) conformation about the internal peptide bond. In the type-I (3-turn a helical i+1 residue and a quasi-helical 1+2 residue are found, whereas in the type-II (3-turn the i+1 residue is semi-extended and the 1+2 residue is also quasi-helical but left-handed. This latter corner position may be easily occupied by the achiral Gly or a D-amino acid residue. 

There is still no way of determining whether or not a given desmosine crosslinks 1, 2, 3, or 4 polypeptide chains of elastin. Based on model studies, however, the most favorable arrangement would be expected if only two chains are crosslinked together by a desmosine (19). This extends from observations that polyalanyl-rich peptides typically favor a-helical conformations and that it is difficult to interconnect more than two polypeptide chains around any given desmosine. With regard to the other amino acids that could potentialy crosslink elastin, the exact number of dehydrolysinonorleucine, dehydromerodesmosine and allysine aldol residues that are involved as intra- or intermolecular crosslinks, and the extent to which these residues may be reduced to form stable crosslinks is not known. 

When two or more almost fully extended polypeptide chains are brought together side by side, regular hydrogen bonds can form between the peptide backbone amide NH and the carbonyl oxygen of adjacent chains. Such an arrangement is called a p sheet. Since each backbone peptide group has its... 

Studies with other poly(/3-i -aspartate)s demonstrate that these polymers not only adopt conformational patterns that are similar to poly(a-amino acids), but that they exhibit greater conformational versatility. The range of conformations now include extended chain structures, arranged as antiparallel packings that come about by stretching poly(a-methyl-/3-L-aspartate) films in boiling water.209 In solution, the helix—coil conformational transition is a phenomenon common to the whole family of poly-(a-alkyl-/3-L-aspartates).210 The ordered conformation is responsive to environmental factors such as temperature and solvent in much the same way as for poly(a-peptides). 

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