All-cis helical polypeptides.
The possibility of all-cis open-chain polypeptides is rarely addressed, owing to three main reasons, namely, (i) the extreme scarcity of cis peptide bonds in naturally occurring proteins and peptides, (ii) the lesser thermodynamic stability (by about 2.5 kcal/mol) of cis amide bonds with respect to their trans counterparts, and (iii) widely held preconceptions about the so-called "steric clash" between lateral chains borne by two successive alpha carbons. Quantum-chemistry calculations performed on alanine tridecamers show how the latter constraints can be efficiently relieved through proper phi/psi adjustments along the backbone, leading to several helical arrangements--presumably the only permitted regular structures. Four more-or-less regular helices were thus characterized, one of them, a superhelix, exhibiting intramolecular hydrogen bonds. Understanding and anticipating all-cis open-chain structures not only make use of the classical Ramachandran maps at each C alpha i, relating to E = f(phi i,psi i), but also require the profile of a new kind of conformational dependence, the plaque maps, relating to E = f(phi i,psi i-1). The obvious coupling between two such maps enforces conformational dependence between two consecutive C alpha's, somewhat questioning in this context the customary "local effects", and presumably reducing the whole chain plasticity. Whereas cis thermodynamic penalty cannot be abolished locally, energy clues indicate that assembling cis-prepared building units is an exothermic process. Besides, once built up, the all-cis backbone should be difficult to unlock, thus affording reasonable kinetic stability.
Poteau
Romuald
R
Laboratoire de Physique et Chimie des Nano-Objets (UMR5215, CNRS-UPS-INSA), IRSAMC, Institut National des Sciences Appliquées, 31077 Toulouse Cedex 4, France.
Trinquier
Georges
G
D003198:Computer Simulation; D008956:Models, Chemical; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013237:Stereoisomerism
D010455:Peptides