Brief Guide for Preparing a Peptide-Drug Conjugate.

Peptide-Drug Conjugates (PDCs) have recently emerged as interesting hybrids constructs not only for targeted therapy, but also for the early diagnosis of different pathologies. In most cases, the crucial step in the PDCs synthesis is the final conjugation step, where a specific drug is bound to a particular peptide/peptidomimetic targeting unit. Thus, this concept paper aims to give a short guide for determining the finest conjugation reaction, by considering in particular the reaction conditions, the stability of the linker and the major pros and cons of each reaction. Based on the recent PDCs reported in literature, the most common and efficient conjugation methods will be systematically presented and compared, generating a short guide to consult while planning the synthesis of a novel peptide-drug conjugate.