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Helix–helix interconversion rates of short 13C-labeled helical peptides as measured by dynamic NMR spectroscopy

✍ Scribed by Matthew Kubasik; James Kotz; Christopher Szabo; Theresa Furlong; Justin Stace


Publisher
Wiley (John Wiley & Sons)
Year
2005
Tongue
English
Weight
208 KB
Volume
78
Category
Article
ISSN
0006-3525

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✦ Synopsis


Abstract

The rates at which a peptide hexamer and a peptide octamer interconvert between left‐ and right‐handed helical forms in CD~2~Cl~2~ solution have been characterized by ^13^C dynamic NMR (DNMR) spectroscopy. The peptide esters studied are Fmoc–(Aib)~n~–OtBu (n = 6 and 8), where Fmoc is 9‐fluorenylmethyoxycarbonyl and Aib is the strongly helix‐forming residue α‐aminoisobutyric acid. Because the Aib residue is itself achiral, homooligomers of this residue form a 50/50 mixture of enantiomeric 3~10~‐helices in solution. It has been demonstrated (R.‐P. Hummel, C. Toniolo, and G. Jung, Angewandte Chemie International Edition, 1987, Vol. 26, pp. 1150–1152) that oligomers of Aib interconvert on the millisecond timescale. We have performed lineshape analysis of ^13^C‐NMR spectra collected for our peptides enriched with ^13^C at a single residue. Rate constants for the octamer range from 6 s^−1^ at 196 K to about 56,500 s^−1^ at 320 K. At all temperatures, the hexamer interconverts about three times faster than the octamer. Eyring plots of the data reveal experimentally indistinguishable Δ__H__‡ values for the hexamer and octamer of 37.8 ± 0.6 and 37.6 ± 0.4 kJ mol^−1^ respectively. The difference in the rates of interconversion is dictated by entropic factors. The hexamer and octamer exhibit negative Δ__S__‡ values of −29.0^−1^ ± 2.5 and −37.3 ± 1.7 J K^−1^ mol^−1^, respectively. A mechanism for the helix–helix interconversion is proposed. and calculated Δ__G__‡ values are compared to the estimate for a decamer undergoing a helix–helix interconversion. © 2005 Wiley Periodicals, Inc. Biopolymers 78: 87–95, 2005