title: Peptide B12: emerging trends at the interface of inorganic chemistry, chemical biology and medicine.
abstract: The sophisticated and efficient delivery of vitamin B(12) ("B(12)") into cells offers promise for B(12)-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 B(12) surrogates. Vitamin B(12) 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 B(12) dependent enzymes are potential suppressors of fast proliferating cancer cells. This perspective article focuses on the design and study of backbone modified B(12) derivatives, particularly on peptide B(12) derivatives. Peptide B(12) 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.
authors.affiliation: Institute of Inorganic Chemistry, University of Zürich, Winterthurerstrasse 190, 8057 Zürich, Switzerland. zelder@aci.uzh.ch
authors.forename: Felix
authors.initials: F
authors.lastname: Zelder
authors.forename: Kai
authors.initials: K
authors.lastname: Zhou
authors.forename: Marjorie
authors.initials: M
authors.lastname: Sonnay
mesh_terms: D015195:Drug Design; D006801:Humans; D019751:Intramolecular Transferases / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
chemical_list: D010455:Peptides; D011392:Proline; D019751:Intramolecular Transferases; C021570:methylaspartate mutase; D014805:Vitamin B 12