Peptide affinity label derivatives

The chemical structures and biological activities of hundreds of opioid analgesics derived from the prototype opioid drug morphine are most comprehensively described in two books published in 1986, one entitled Opioid Analgesics, Chemistry and Receptors by Casy and Parfitt [1] and the other entitled Opiates by Lenz et al. [2]. Follow-up articles include those by Casy in 1989, entitled Opioid Receptors and their Ligands Recent Developments [3] which also includes sections on opioid peptides, affinity labelling and opioid receptor subtypes Rees and Hunter in 1990 [4] covering the... 

The diazomethyl ketone functional group was first observed to be an affinity label by Buchanan and co-workers who showed that the antibiotic azaserine, an O-diazoacetyl derivative, 9 inhibited an enzyme in the biosynthesis of purine by alkylation of a cysteine residue. 10 The acid protease pepsin was then observed to be inhibited by peptidyl diazomethyl ketones in the presence of copper ions with the resulting esterification of an aspartate residue. 11 Two peptidyl diazomethyl ketones, Z-Phe-CHN2 and Z-Phe-Phe-CHN2, were found to irreversibly inactivate papain, a cysteine protease. 12 Since these reports, many peptidyl diazomethyl ketones have been prepared primarily as inhibitors of various cysteine proteases. 7 Peptidyl diazomethyl ketones are also synthetic intermediates and have been used to prepare chloromethyl ketones (Section 15.1.3), 13 bromomethyl ketones (Section 15.1.3), acyloxymethyl ketones, 14 and (i-peptides. 15 A few peptidyl diazoalkyl ketones have been reported. 16,17 ... 

Peptide-based affinity labels have been principally photoaffinity labels, including the azide derivatives of several enkephalin analogs and CTP (see Refs. 286,594 for detailed reviews). As noted earlier (Section 5.11.2), the use of photoaffinity labels, however, has been limited because opioid receptors are susceptible to inactivation by UV irradiation (643). 

MIPD has also been utilized for potential diagnostic use in Alzheimer s disease. Willbold et al. used the all-o version of Ap(l-42) amyloid peptide as a target to screen a commercial phage display library to generate a dominant consensus sequence whose all D-amino acid analog o-pep bound the native AP(l-42) sequence with submicromolar affinity [181]. In addition, a fluorescein-labeled derivative of o-pep was shown to stain native Ap amyloid fibrils specifically, suggesting it may be useful as a diagnostic probe for amyloid plaques. 

Most of the methodologies used and problems encountered with halo-ketones as affinity labels are covered by considerations of bromopyruvate, haloacetol phosphates, and haloketone derivatives of pyridine nucleotides. Similar information is gained from numerous elegant studies in which halomethylketone derivatives of amino acids and peptides have been used as affinity labels for proteases. These investigations are excluded from the present article, since they are considered elsewhere in this volume. ... 

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