Synthesis of cyclic herpes simplex virus peptides containing 281-284 epitope of glycoprotein D-1 in endo- or exo-position

We have prepared two types of cyclopeptides containing the (281)DPVG(284) s equence from the 276-284 region of glycoprotein gD-1 of the Herpes simplex virus (HSV). The syntheses were performed by solid phase methodology using MBHA or BHA resin and orthogonal protection schemes. Head-to-side-chain cyc lization included the N-terminal part of the epitope, while side-chain-to-s ide-chain lactam bridge formation resulted in a peptide containing a C-term inal cycle. Peptides elongated by Cys at the N-terminal of the sequence wer e also prepared. Boc chemistry using Fmoc and OFm orthogonal protection was applied for on-resin cyclization. Based on the orthogonality of Bzl and cH ex esters under a 1 M TMSOTf-thioanisole/TFA cleavage condition, a new appr oach for the cyclization on BHA-resin has also been developed. Preliminary studies on solution conformation of the cyclic peptides by CD spectroscopy indicated the importance of the location and the size of the cycle within t he epitope sequence. Copyright (C) 1999 European Peptide Society and John W iley & Sons. Ltd.