Chatterjee, Sunanda and Roy, Rituparna Sinha and Balaram, P (2007) Expanding the polypeptide backbone: hydrogen-bonded conformations in hybrid polypeptides containing the higher homologues of alpha-amino acids. In: JOURNAL OF THE ROYAL SOCIETY INTERFACE, 4 (15). pp. 587-606.
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Half a century has passed since the hydrogen-bonded secondary structures of polypeptides and proteins were first recognized. An extraordinary wealth of conformational information is now available on peptides and proteins, which are formed of alpha-amino acid residues. More recently, the discovery of well-folded structures in oligopeptides containing beta-amino acids has focused a great deal of current interest on the conformational properties of peptides constructed from higher homologues (omega) of alpha-amino acids. This review examines the nature of intramolecularly hydrogen-bonded conformations of hybrid peptides formed by amino acid residues, with a varying number of backbone atoms. The beta-turn, a ubiquitous structural feature formed by two residue (alpha alpha) segments in proteins and peptides, is stabilized by a 10-atom (C-10) intramolecular 4 -> 1 hydrogen bond. Hybrid turns may be classified by comparison with their alpha alpha counterparts. The available crystallographic information on hydrogen-bonded hybrid turns is surveyed in this review. Several recent examples demonstrate that individual omega-amino acid residues and hybrid dipeptide segments may be incorporated into the regular structures of alpha-peptides. Examples of both peptide helices and hairpins are presented. The present review explores the relationships between folded conformations in hybrid sequences and their counterparts in all alpha-residue sequences. The use of stereochemically constrained omega-residues promises to expand the range of peptide design strategies to include omega-amino acids. This approach is exemplified by well-folded structures like the C-12 (alpha gamma) and C-14 (gamma gamma) helices formed in short peptides containing multiply substituted gamma-residues. The achiral gamma-residue gabapentin is a readily accessible building block in the design of peptides containing gamma-amino acids. The construction of globular polypeptide structures using diverse hybrid sequences appears to be a realistic possibility.
|Item Type:||Journal Article|
|Additional Information:||Copyright for this article belongs to Royal Society|
|Keywords:||hydrogen bonds; peptide conformation; hybrid peptides; omega-amino acids; backbone-homologated amino acids|
|Department/Centre:||Division of Biological Sciences > Molecular Biophysics Unit|
|Date Deposited:||31 Dec 2008 07:23|
|Last Modified:||19 Sep 2010 04:58|
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