ABSTRACT
Synthetic methods of peptide chemistry have played a significant role in the spectacular development of antimicrobial peptide research over the last two decades. Interest in antibiotic peptides coincided with-and benefited from-a period when synthetic peptide chemistry had achieved an unprecedented level of proficiency. In his 1984 Nobel lecture (1), Bruce Merrifield referred to the synthetic work on cecropins currently being done at his laboratory as an example of the achievements in solid phase synthetic methodology. Although many substantial discoveries in antimicrobial peptide research have been possible only through molecular biology methods, as the chapters in this volume illustrate, it is no less true that many of those findings could be confirmed and developed further only by ready access to synthetic versions and analogs of the original antimicrobial sequences. In this chapter we will briefly consider the basic features of synthetic chemistry pertinent to antimicrobial peptides and then review some of its applications to areas such as structure confirmation, validation of putative antimicrobial sequences, design of analogs to study structure-activity relationships and mechanisms of action, or de novo design.
