Peptides photolabile linkers

An interesting application of the 3-methoxybenzoin-based photolabile linker has been described in which the dithiane, ( )-(3- 2-(l,3-dithian-2-yl)-l-[(9-fluorenylmethoxy-carbonyl)oxy]-2-phenylethyl)benzyl)oxy] acetic acid (126, Scheme 33), a transiently masked form of the caging moiety, is incorporated into a peptide chain generated by solid-phase synthesis. 248 ... 

The encoding tags are halophenoxy derivatives of aliphatic alcohols and are attached to either a photolabile linker as a carbonate or an oxidatively cleavable linker as an ether. The photolabile linker/tag complex is especially well suited to encode peptide libraries through attachment to approximately 1% of the amino groups of each amino acid synthon at eachstage of the synthesis. For structure determination, the tags are released by photolysis at 360 nM. 

A sequential solid-phase peptide synthesis has been developed which makes use of both a photolabile linker and a photolabile protecting group (Scheme 8). The system is based on a tert-butyl ketone-derived linker, which is sensitive to... 

Giese also suggested a solid phase peptide synthesis strategy using both the photolabile linker 34 and the NVOC protecting group to avoid the use of common... 

Photolabile carbonate supports 2j have been constructed by attachment of a preformed handle consisting of the reaction scaffold and an ortho-nitrobenzyl alcohol photolabile linker to PEG-PS [121]. Peptide sequences were constructed from the scaffold, and final products were liberated in a form suitable for direct biological screening by irradiation at 365 nm in an aqueous medium. 

Fig. 8 Photo-triggered peptide self-assembling system designed by Imperiali s group. In this molecular system, fibril-inhibitory unit was attached to the amyloidogenic unit through photolabile linker. (Adapted from [44])...

Another aminomethyl PS resin supported o-nitrobenzyl photolabile hnker 1.23 (80) has been employed for the synthesis of heterocycles such as thiazohdinones. Attachment to the resin is through an acid or aldehyde group and photolytic cleavage is performed in 5% dimethyl sulfoxide (DMSO)-aqueous buffer to facilitate the biological testing of the final compound. A photolabile hydroxyl linker 1.24 (81), again supported on aminomethyl PS resin, has been used to synthesize carbohydrate and peptide derivatives in SP. The easily prepared diol linker 1.25 (82) allowed the attachment of aldehydes as acetals and their photo induced release using standard conditions. 

The solid phase synthesis of peptides using a photolabile nitrobenzyl linker was first reported by Rich [4] in 1973. He used a nitro-funchonalized Merrifield resin (1) and attached a Boc-protected amino acid by refluxing it with base. The peptide chain was synthesized using Merrifield s procedure [5] and the synthesized peptide was cleaved from the resin using UV irradiation (350nm) in methanol (Scheme 17.2). 

Photolabile a-halophenacyl resins (lo-lq) have been used to form an acid-stable anchor to the carboxyl group of amino acids prior to peptide elongation [97]. Cleavage of the final products was achieved by irradiation with light of wavelength 350 nm. Related linkers that differ in the mode of attachment to the resin have been reported [98-100]. Carboxylic acids can also be released by treatment of these supports with base [101] or cyanide ion [102] and peptide hydrazides have been released by treatment with hydrazine [97,103]. 

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