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.