Abstract

Glycoproteins of the mammalian oocyte's extracellular integument, the zona pellucida, are female-specific macromolecules important for sperm-egg interaction and, potentially, contraceptive vaccine development. Functioning as ligands for sperm-associated zona-binding proteins, specific zona glycoproteins are known to mediate sperm-zona adhesion and the subsequent zona-induced sperm acrosome reaction, two early events in the fertilization process. According to the current paradigm, carbohydrates are the structural elements of zona macromolecules responsible for ligand activity. The zonae of diverse species share a common architecture being comprised of three glycoproteins, termed pZPA, pZPB and pZPC. Using the pig as a model, we have determined that pZPB-pZPC heterocomplexes are high affinity ligands for sperm-associated zona receptors. This project seeks to characterize the structures of pZPB and pZPC N- and O-linked sugar chains and elucidate their role in ligand-receptor interactions. The structures of N-linked oligosaccharides released from intact pZPB and pZPC glycoproteins and site-specific glycopeptides are currently being investigated using MALDI-MS in combination with sequential exoglycosidase digestions. These data will provide fresh insights concerning structure-function relationships of zona carbohydrates.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
3P41RR000480-28S1
Application #
6258877
Study Section
Project Start
1997-06-01
Project End
1999-11-30
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
28
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
Michigan State University
Department
Type
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824

  Publications

Peri, S P; Bhadti, V S; Somerville-Armstrong, K S et al. (1999) Affinity reagents for cross-linking hemoglobin: bis(phenoxycarbonylethyl)phosphinic acid (BPCEP) and bis(3-nitrophenoxycarbonylethyl)phosphinic acid (BNCEP). Hemoglobin 23:1-20
Chen, H M; Sood, R; Hosmane, R S (1999) An efficient, short synthesis and potent anti-hepatitis B viral activity of a novel ring-expanded purine nucleoside analogue containing a 5:7-fused, planar, aromatic, imidazo[4,5-e][1,3]diazepine ring system. Nucleosides Nucleotides 18:331-5
Bretner, M; Beckett, T D; Sood, R K et al. (1999) Substrate/inhibition studies of bacteriophage T7 RNA polymerase with the 5'-triphosphate derivative of a ring-expanded ('fat') nucleoside possessing potent antiviral and anticancer activities. Bioorg Med Chem 7:2931-6
Agasimundin, Y S; Mumper, M W; Hosmane, R S (1998) Inhibitors of glycogen phosphorylase b: synthesis, biochemical screening, and molecular modeling studies of novel analogues of hydantocidin. Bioorg Med Chem 6:911-23
Hosmane, R S; Peri, S P; Bhadti, V S et al. (1998) Bis[2-(4-carboxyphenoxy)carbonylethyl]phosphinic acid (BCCEP): a novel affinity reagent for the beta-cleft modification of human hemoglobin. Bioorg Med Chem 6:767-83
Rajappan, V P; Hosmane, R S (1998) Analogues of azepinomycin as inhibitors of guanase. Nucleosides Nucleotides 17:1141-51
Hosmane, R S; Hong, M (1997) How important is the N-3 sugar moiety in the tight-binding interaction of coformycin with adenosine deaminase? Biochem Biophys Res Commun 236:88-93
Lopez-Lara, I M; Orgambide, G; Dazzo, F B et al. (1993) Characterization and symbiotic importance of acidic extracellular polysaccharides of Rhizobium sp. strain GRH2 isolated from acacia nodules. J Bacteriol 175:2826-32
Watson, J T; Kayganich, K (1989) Novel sample preparation for analysis by electron capture negative ionization mass spectrometry. Biochem Soc Trans 17:254-7
Kassel, D B; Kayganich, K A; Watson, J T et al. (1988) Utility of ion source pretreatment with chlorine-containing compounds for enhanced performance in gas chromatography/negative ionization mass spectrometry. Anal Chem 60:911-7

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