Synthesis of the trypsin fragment 10–25/75–88 of mouse nerve growth factor*

Abstract

Cyanogen bromide cleavage followed by trypsin digestion of mouse nerve growth factor (NGF) allowed the isolation of a double chain unsymmetrical cystine peptide of high neurotrophic activity. The presence of tryptophan residues severely limits the synthetic approaches for selective disulfide bridging. The strategy applied for such a purpose as well as the preparation of the suitably protected tetradecapeptide corresponding to sequence 75–88 as key intermediate for the synthesis of the NGF fragment 10–25/75–88 are described.

Stepwise Construction of Disulfides in Peptides

“…Peptides with a free thiol can be treated with di‐ tert ‐butylazodicarboxylate (DBAD) to provide an isolable sulfenylhydrazide intermediate, which, when combined with another free thiol‐containing peptide, will form a two‐chain heterodimeric product, with the newly formed disulfide serving as the interchain linkage . A similar scheme was developed with the S ‐carbomethoxysulfenyl (Scm) protecting group to synthesize the same class of two‐chain peptides .…”