Sj. Stachel et al., STABILIZATION OF A C-7 EQUATORIAL GAMMA-TURN IN DMSO-D(6) BY A DITRYPTOPHAN CROSS-LINK, Bioorganic & medicinal chemistry, 6(9), 1998, pp. 1439-1446
Covalent crosslinks can control local peptide conformation. In tripept
ide sequences of the general formula Cys-Xxx-Cys, cysteine disulfides
have been previously shown to enforce a C-7 equatorial gamma-turn conf
ormation (also referred to as an inverse gamma-turn). Much less is kno
wn about the effects of dityrosine and ditryptophan crosslinks on loca
l peptide structure. In a series of tripeptides, ditryptophan crosslin
ks were formed using the two-step process of acid-promoted Mannich dim
erization followed by oxidative aromatization. In these peptides, with
the general formula Trp-Xxx-Trp (Xxx not equal Gly), ditryptophan cro
sslinks were found to stabilize a C-7 equatorial gamma-turn conformati
on in DMSO-d(6). Rigorous support for a C-7 equatorial conformation in
the crosslinked sequence Trp-Pro-Trp came from a variety of H-1 NMR e
xperiments and molecular modelling. Interproton distances were derived
from NOE buildups that were determined through a series of double pul
sed field gradient spin echo (DPFGSE) experiments. In addition, the sm
all temperature dependence of the i + 2 NH chemical shifts (Delta delt
a/Delta T < 2 ppm/degrees C) provided further support for the intramol
ecular hydrogen bond which defines a gamma-turn. (C) 1998 Elsevier Sci
ence Ltd. All rights reserved.