Azobenzene-Based ω-Amino Acids and Related Building Blocks: Synthesis, Properties, and Application in Peptide Chemistry

Abstract

Azobenzenes are widely used as optical triggers for the development of photoresponsive materials. Starting from the literature-known w-amino acids 4,4¢-APB 1a and 4,4¢-AMPB 2a, metasubstituted analogues were synthesized for the incorporation into peptides and proteins. While 4,4¢-APB 1a requires special chemistry for peptide synthesis, an Fmoc/t-Bu protecting group strategy is applicable for 3,3¢-APB 1b. The versatility of this and other novel azobenzene w-amino acids is demonstrated by the preparation of cyclic photoswitchable phosphopeptides with the binding motif pTyr-Val-Asn-Val. Photochromic properties of the azo subunits and of the corresponding peptides are also presented.

Light‐Switchable Peptides with a Hemithioindigo Unit: Peptide Design, Photochromism, and Optical Spectroscopy

“…Further structural flexibility of the photoswitch can be achieved by shifting the aminomethylene group into the meta position in the ω‐amino acid mHTI (Tables and ). Generally, libraries were designed to investigate the substitution pattern of the photoswitch and surrounding amino acid sequence in cyclic peptides, leading to the optimization of photochromic, conformational, and biophysical properties on route toward biological applications and folding studies …”

“…Basic reaction conditions allowed unwanted retro‐aldol reactions, and silane scavengers gave decomposition products through hydride attack at the α,β‐unsaturated carbonyl moiety . Nevertheless, reliable protocols for solid‐phase peptide synthesis were developed, and the coupling reagents 1‐ethyl‐3‐(3‐dimethylaminopropyl)carbodiimide (EDC), N,N,N′,N′‐tetramethyl‐O‐(1H‐benzotriazol‐1‐yl)uronium hexafluorophosphate (HBTU), 1‐[bis(dimethylamino)methylen]‐5‐chlorobenzotriazolium 3‐oxide hexafluorophosphate (HCTU), benzotriazol‐1‐yloxy)tripyrrolidinophosphonium hexafluorophosphate (PyBOP), and diphenylphosphoryl azide (DPPA) were successfully employed …”

Enhanced user-control of small molecule drug release from a poly(ethylene glycol) hydrogel via azobenzene/cyclodextrin complex tethers

“…S3a) was synthesized by solid phase peptide synthesis (Tribute) and contained N-terminal acetylated 3-[[4-[amino]methyl)phen-yl]diazenyl]benzoic acid (3,4′-AMPB) 27,28 . This particular azobenzene derivative was selected on account of its previously reported long half-life of thermal relaxation, which may be related, in part, to intermolecular interactions between the meta-substituent and the peptide backbone 29 .…”

Photocontrol of Contracting Muscle Fibers

“…The recently described nNOS-derived, photoswitchable peptide ligand 1 of a-1-syntrophin contains the azobenzenew-amino acid 3-((4'-aminomethyl)phenylazo)benzoic acid (3,4'-AMPB), [4] which in its trans form led to a ligand that showed no affinity to the PDZ domain of a-1-syntrophin while photoisomerization to the cis form resulted in a remarkable affinity of the peptide (K D = 10.6 mm).…”