Peptide B12: emerging trends at the interface of inorganic chemistry, chemical biology and medicine

Abstract

The sophisticated and efficient delivery of vitamin B12 (“B12”) into cells offers promise for B12-bioconjugates in medicinal diagnosis and therapy. It is therefore surprising that rather little attention is presently paid to an alternative strategy in drug design: the development of structurally perfect, but catalytically inactive semi-artificial B12 surrogates. Vitamin B12 cofactors catalyse important biological transformations and are indispensible for humans and most other forms of life. This strong metabolic dependency exhibits enormous medicinal opportunities. Inhibitors of B12 dependent enzymes are potential suppressors of fast proliferating cancer cells. This perspective article focuses on the design and study of backbone modified B12 derivatives, particularly on peptide B12 derivatives. Peptide B12 is a recently introduced class of biomimetic cobalamins bearing an artificial peptide backbone with adjustable coordination and redox-properties. Pioneering biological studies demonstrated reduced catalytic activity, combined with inhibitory potential that is encouraging for future efforts in turning natural cofactors into new anti-proliferative agents.