Fmoc-Gln(Trt)-OH

Fmoc-Gln(Trt)-OH

A 'conovenomic' analysis of the milked venom from the mollusk-hunting cone snail Conus textile--the pharmacological importance of post-translational modifications.[Pubmed:24055806]

Peptides. 2013 Nov;49:145-58.

Cone snail venoms provide a largely untapped source of novel peptide drug leads. To enhance the discovery phase, a detailed comparative proteomic analysis was undertaken on milked venom from the mollusk-hunting cone snail, Conus textile, from three different geographic locations (Hawai'i, American Samoa and Australia's Great Barrier Reef). A novel milked venom conopeptide rich in post-translational modifications was discovered, characterized and named alpha-conotoxin TxIC. We assign this conopeptide to the 4/7 alpha-conotoxin family based on the peptide's sequence homology and cDNA pre-propeptide alignment. Pharmacologically, alpha-conotoxin TxIC demonstrates minimal activity on human acetylcholine receptor models (100 muM, <5% inhibition), compared to its high paralytic potency in invertebrates, PD50 = 34.2 nMol kg(-1). The non-post-translationally modified form, [Pro](2,8)[Glu](16)alpha-conotoxin TxIC, demonstrates differential selectivity for the alpha3beta2 isoform of the nicotinic acetylcholine receptor with maximal inhibition of 96% and an observed IC50 of 5.4 +/- 0.5 muM. Interestingly its comparative PD50 (3.6 muMol kg(-1)) in invertebrates was ~100 fold more than that of the native peptide. Differentiating alpha-conotoxin TxIC from other alpha-conotoxins is the high degree of post-translational modification (44% of residues). This includes the incorporation of gamma-carboxyglutamic acid, two moieties of 4-trans hydroxyproline, two disulfide bond linkages, and C-terminal amidation. These findings expand upon the known chemical diversity of alpha-conotoxins and illustrate a potential driver of toxin phyla-selectivity within Conus.

Novel N omega-xanthenyl-protecting groups for asparagine and glutamine, and applications to N alpha-9-fluorenylmethyloxycarbonyl (Fmoc) solid-phase peptide synthesis.[Pubmed:8914163]

Pept Res. 1996 Jul-Aug;9(4):166-73.

The N alpha-9-fluorenylmethyloxycarbonyl (Fmoc), N omega-9H-xanthen-9-yl (Xan), N omega-2-methoxy-9H-xanthen-9-yl (2-Moxan) or N omega-3-methoxy-9H-xanthen-9-yl (3-Moxan) derivatives of asparagine and glutamine were prepared conveniently by acid-catalyzed reactions of appropriate xanthydrols with Fmoc-Asn-OH and Fmoc-Gln-OH. The Xan and 2-Moxan protected derivatives have been used in Fmoc solid-phase syntheses of several challenging peptides: a modified Riniker's peptide to probe tryptophanalkylation side reactions, Briand's peptide to assess deblocking, at the N-terminus and Marshall's ACP (65-74) to test difficult couplings. Removal of the Asn and Gln side-chain protection occurred concomitantly with release of peptide from the support, under the conditions for acidolytic cleavage of the tris(alkoxy)benzylamide (PAL) anchoring linkage by use of trifluoroacetic acid/scavenger mixtures. For each of the model peptides, the products obtained by the new protection schemes were purer than those obtained with N omega-2,4,6-trimethoxybenzyl (Tmob) or N omega-triphenylmethyl (Trt) protection for Asn and Gln.