The document describes a novel resin with a photoreactive linker that allows for the synthesis of peptides and glycopeptides using solid phase peptide synthesis. Upon illumination with UV light in the presence of a mercaptan, a peptide-α-thioester is generated by direct photorelease with minimal epimerization. Initial results show that thioesters can be generated either in solution or by direct photorelease from the resin with negligible epimerization. The method is also shown to work for the photochemical thioesterification of glycopeptides for use in large glycopeptide synthesis by native chemical ligation.

1. Photochemical Preparation of (Glyco)Peptide- α -Thioesters Tyrone Hogenauer and Dr. Katja Michael The University of Texas at El Paso EXPERIMENTAL ABSTRACT RESULTS FUTURE WORK REFERENCES We describe the development of a novel resin with a photoreactive N-acylnitroindoline linker, that allows for the synthesis of peptides and glycopeptides using standard Fmoc/t-Bu SPPS. Upon illumination with UV-light, in the presence of a mercaptan, the peptide- α - thioester is generated by direct photo-release with minimal epimerization. Contact information: tjhogenauer@miners.utep.edu; kmichael@utep.edu Acknowledgements UTEP College of Science UTEP Student Government Association American Chemical Society BACKGROUND Mechanism of photochemical acylation: Above: RP HPLC profile of crude peptide thioester, A) by direct photorelease from 7 B) by photoesterification of 10 in solution. A byproduct, Fmoc-Val-Ala-Gly-OH, elutes at 11.5 min.Right: RP HPLC profiles of crude photothioesterifications in DMSO. A) Photorelease of 14 from 8 ; B) Photorelease of 15 from 9 ; C) Coinjection of both reaction mixtures. The asterisk depicts material eluting at the beginning of the column wash with 85% acetonitrile. • Thioesters are generated either in solution or by direct photorelease from the beads • Negligible epimerization Glycopeptide partial sequence Gly 411 - Pro 419 of gp120: • Photochemical thioesterification of glycopeptides • Their use in large glycopeptide synthesis by native chemical ligation 1. G. Papageorgiou and J. E. T. Corrie, Tetrahedron , 2000, 56, 8197. (b) J. Morrison, P. Wan, J. E. T. Corrie and G. Papageorgiou, Photochem. Photobiol. Sci ., 2002, 1, 960; (c) G. Papageorgiou, D. Ogden, G. Kelly and J. E. T. Corrie, Photochem. Photobiol. Sci ., 2005, 4, 887. 2. S. Pass, B. Amit and A. Patchornik, J. Am. Chem. Soc., 1981, 103, 7674. 3. K. C. Nicolaou, B. S. Safina and N. Winssinger, Synlett , 2001, SI, 900. 4. T. J. Hogenauer, K. Michael, Org. Biomol. Chem ., 2007, 5, 759–762.