Premium
How To Stabilize or Break β ‐Peptidic Helices by Disulfide Bridges: Synthesis and CD Investigation of β ‐Peptides with Cysteine and Homocysteine Side Chains
Author(s) -
Jacobi Albrecht,
Seebach Dieter
Publication year - 1999
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/(sici)1522-2675(19990804)82:8<1150::aid-hlca1150>3.0.co;2-o
Subject(s) - chemistry , side chain , thioether , cysteine , stereochemistry , circular dichroism , peptide , methionine , nuclear magnetic resonance spectroscopy , hydantoin , serine , solid phase synthesis , valine , crystallography , amino acid , organic chemistry , biochemistry , enzyme , polymer
all‐ L ‐ β 3 ‐Penta‐, hexa‐, and heptapeptides with the proteinogenic side chains of valine, leucine, serine, cysteine, and methionine have been prepared by previously described procedures ( 12 , 13 , 14 , 15 ; Schemes 2 – 5 ). Thioether cleavage with Na/NH 3 in β ‐HMet residues has also provided a β 3 ‐hexapeptide with homocysteine (CH 2 CH 2 S) side chains ( 13e ). The HS−(CH 2 ) n groups were positioned on the β ‐peptidic backbone in such a way that, upon disulfide‐bridge formation, the corresponding β ‐peptide was expected to maintain either a 3 1 ‐helical secondary structure ( 1 , 2 ) ( Fig. 1 ) or to be forced to adopt another conformation ( 3 , 4 ). The 13‐, 17‐, 19‐, and 21‐membered‐ring macrocyclic disulfide derivatives and their open‐chain precursors, as well as all synthetic intermediates, were purified (crystallization, flash or preparative HPL chromatography; Fig. 5 ) and fully characterized (m.p., [ α ] D , CD, IR, NMR, FAB or ESI mass spectroscopy, and elemental analysis, whenever possible; Fig. 2 and Exper. Part ). The structures in MeOH and H 2 O of the new β ‐peptides were studied by CD spectroscopy ( Figs. 3 and 4 ), where the characteristic 215‐nm‐trough/200‐nm‐peak pattern was used as an indicator for the presence or absence of ( M )‐ 3 1 ‐helical conformations. A CH 2 −S 2 −CH 2 and, somewhat less so, a (CH 2 ) 2 −S 2 −(CH 2 ) 2 bracket between residues i and i +3 ( 1 vs . 12d , and 2 vs . 13e in Fig. 3 ) give rise to CD spectra which are compatible with the presence of 3 1 ‐helical structures, while CH 2 −S 2 −CH 2 brackets between residues i and i +2 ( 3 vs . 14c ) or i and i +4 ( 4 vs . 15c in Fig. 4 ) do not.