Bio-orthogonal Reactions: Potential Tools of Current Medicinal Chemistry
Hugo Cerecetto, PhD
Summary
The developments of the last decade in aqueous chemoselective reactions, bio-orthogonal reactions, for biomolecules modifications have provided tools to decorate them with some structural frameworks derived from probes, drugs, reactive tags, etc., without significantly perturbing their native biochemical functions.
These transformations have been used, among others:
– for the in vivo spatial and temporal control of biomolecules,
– for imaging,
– for the elucidation of the role of post-translational modifications and,
– for drug-delivery.
Consequently, the bioorthogonal reactions become in fundamental tools of current medicinal chemistry.
This course will describe the topic involving the following aspects:
Content
1) Introduction. History.
2) Principles of bio-orthogonal reactions. a) Procedures: i) Involving metabolic or protein engineering; ii) Not involving metabolic or protein engineering. b) Bio-orthogonality requirements: i) Selectivity; ii) Biological inertness; iii) Chemical inertness; iv) Kinetic; v) Reaction biocompatibility; vi) Accessible engineering.
2.1) 1,3-Dipolar cycloadditions. a) Background. b) Copper-free click chemistry. c) Nitrone dipole cycloaddition. d) Photoclick 1,3-dipolar cycloaddition. e) Other 1,3-dipole.
2.2) Diels–Alder reactions. a) “Normal” electron demand. b) Inverse electron demand.
2.3) Other. a) Staudinger ligation. b) Transition metal catalysis. c) Reactions with 2-cyanobenzothiazoles. d) Ketone/aldehyde condensations.
3) Development of bio-orthogonal reactions.
4) Incorporation of bio-orthogonal moieties into biomolecules.
5) Examples of current applications. a) In the spatial and temporal in vivo control of biomolecules. b) In imaging. c) In the elucidation of post-translational modifications roles. d) In drug-delivery processes (dissociative bio-orthogonal reactions). e) Other examples.