Award Abstract #0502139
International Research Fellowship Program: New Chemical Approaches to Glycopeptide Assembly with Application to the Development of New Antigen Motifs for Vaccine Therapy in HIV

NSF Org:	OISE Office of International Science and Engineering
Initial Amendment Date:	June 3, 2005
Latest Amendment Date:	June 3, 2005
Award Number:	0502139
Award Instrument:	Fellowship
Program Manager:	Susan Parris OISE Office of International Science and Engineering O/D OFFICE OF THE DIRECTOR
Start Date:	December 1, 2005
Expires:	September 30, 2007 (Estimated)
Awarded Amount to Date:	$122700
Investigator(s):	Sarah Tully tully@caltech.edu (Principal Investigator)
Sponsor:	Tully Sarah E Pasadena, CA 91106 / -
NSF Program(s):	EAPSI
Field Application(s):	0203000 Health
Program Reference Code(s):	OTHR, 5980, 5956, 5946, 0000
Program Element Code(s):	7316

ABSTRACT

0502139

Tully

The International Research Fellowship Program enables U.S. scientists and engineers to conduct three to twenty-four months of research abroad. The program's awards provide opportunities for joint research, and the use of unique or complementary facilities, expertise and experimental conditions abroad.

This award will support a twenty-two-month research fellowship by Dr. Sarah E. Tully to work with Dr. Pauline M. Rudd at Oxford University in the United Kingdom.

Most successful vaccines utilize the power of neutralizing antibodies to elicit their effects. Development of such a vaccine for human immunodeficiency virus type 1 (HIV-1) has been hampered due to the ability of envelope protein carbohydrates to protect the peptide backbone from antibody recognition. Recently, human antibody 2G12, an antibody that neutralizes a broad range of HIV-1 isolates, was found to recognize a cluster of carbohydrate moieties on the envelope protein. Generation of a library of glycoproteins similar to the 2G12 antibody would enable the development of different antibodies for HIV-1 vaccine formulations. To create such a library, the PI and her host are developing a convergent synthetic approach for the production of N-linked glycoproteins. Their methodology will have broad-based utility such that glycans, derived from chemical synthesis or from purified glycoprotein hydrolysates, can be attached without protecting groups to a synthetic peptide sequence in water with establishment of the correct b-aspartyl amide linkage present in N-linked glycoproteins. They will then explore the utility of their synthetic approach by constructing a glycoprotein library expressing two mannose-rich glycan structures in spatially-resolved loci as a model for the epitope of 2G12 and as an antigen for the generation of anibodies with similar activity.

Dr. Rudd's laboratory has established numerous international research collaborations with some of the best laboratories in glycobiology.

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