Abstract
Stepwise synthetic assembly of polypeptide chains reversibly linked to polyethylene glycol represents a hybrid between traditional solution and solid‐phase chemistries and combines the inherent advantages of both approaches. The technical simplicity and scalability of the liquid‐phase peptide synthesis method renders it particularly attractive for multiple parallel syntheses, combinatorial approaches and the large‐scale preparation of peptides. The versatile protection strategy based on the N^α^‐fluorenylmethoxycarbonyl group commonly used in solid‐phase peptide synthesis was adapted to the liquid‐phase approach. Fluoride ions were used rather than the conventional organic base piperidine for the repetitive amino‐deprotection step. Using a range of acid‐ and base‐labile linkers between the polymer and the peptide, it was shown that free and fully side‐chain protected peptides can be obtained using our version of the liquid‐phase peptide synthesis method. Protocols for simultaneous multiple syntheses requiring a minimum of equipment are presented and the use of polyethylene glycol‐bound peptides in biochemical binding and functional assay systems is demonstrated. Copyright © 2002 European Peptide Society and John Wiley & Sons, Ltd.