HYDROGEN-BOND-MEDIATED FOLDING IN DEPSIPEPTIDE MODELS OF BETA-TURNS AND ALPHA-HELICAL TURNS

Citation
Ea. Gallo et Sh. Gellman, HYDROGEN-BOND-MEDIATED FOLDING IN DEPSIPEPTIDE MODELS OF BETA-TURNS AND ALPHA-HELICAL TURNS, Journal of the American Chemical Society, 115(21), 1993, pp. 9774-9788
Citations number
55
Categorie Soggetti
Chemistry
ISSN journal
00027863
Volume
115
Issue
21
Year of publication
1993
Pages
9774 - 9788
Database
ISI
SICI code
0002-7863(1993)115:21<9774:HFIDMO>2.0.ZU;2-M
Abstract
The folding of several depsipeptides constructed from alpha-amino acid s [L-proline (P) and L-alanine (A)] and alpha-hydroxy acids [L-lactic acid (L) and glycolic acid (G)] has been examined in methylene chlorid e solution by variable-temperature IR spectroscopy. Additional studies have been conducted in some cases, involving variable-temperature H-1 NMR spectroscopy and molecular mechanics calculations. The depsipepti des include three-residue molecules (PLL, ALL, and PLG) that can form a 13-membered-ring amide-to-amide hydrogen bond, which, for a peptide backbone, would correspond to a single turn of an alpha-helix. These d epsipeptides can also form 10-membered-ring amide-to-ester hydrogen bo nds, which would correspond to beta-trun formation for a peptide backb one. For PLL and PLG, distinct N-H stretch bands can be identified for three folding patterns: non-hydrogen-bonded, beta-turn, and alpha-hel ical turn. IR-based van't Hoff analyses for PLL indicate that the alph a-helical turn and the beta-turn are both modestly enthalpically favor ed relative to the non-hydrogen-bonded state, but neither turn is enth alpically preferred over the other. For PLG, in contrast, the alpha-he lical turn appears to be enthalpically preferred over both of the alte rnative folding patterns. Comparison between PLL and ALL indicates tha t the N-terminal proline residue favors alpha-helical turn formation. The strengths of amide-to-amide and amide-to-ester hydrogen bonds have been compared in the context of a beta-turn geometry by analyzing LG and AG in CH2Cl2. The amide-to-amide hydrogen bond is enthalpically fa vored by ca. 1.6 kcal/mol, but formation of this enthalpically stronge r intramolecular hydrogen bond is more costly entropically. Extrapolat ion from the behavior of these depsipeptides leads us to predict that for tripeptides in a nonpolar environment, a beta-turn will generally be enthalpically preferred over an isolated alpha-helical turn. Beta-t urn folding has previously been widely studied in model peptides and d epsipeptides; however, the present report appears to represent the fir st experimental effort to model formation of a single alpha-helical tu rn.