# The chemical approach towards homogenous glycoprotein preparation and evaluation

> **NIH NIH R35** · STATE UNIVERSITY OF NEW YORK AT ALBANY · 2021 · $365,558

## Abstract

The chemical approach towards homogenous glycoprotein preparation and
evaluation
ABSTRACT – Our long-term goal is to uncover the unknown function of cellular and infectious
prion protein by interrogating individual homogenous prion glycoform. The objective here, is to
develop a class of efficient peptidyl coupling protocols utilizing strained molecules, such as β-
lactone and β-thiolactone, for the construction of previously unattainable targets such as cyclic
tetrapeptides and membrane prion protein. Our central hypothesis, derived from our published
results and preliminary studies described below, is that chemical synthesis can provide the PrPC
and PrPSc strains with high conformational fidelity, which allows prion biological studies to be
carried out with faithful accuracy when interrogating synthetic homogenous glyco-PrPs. The
flexibility of modifying protein construct furnishes previously unavailable tool for evaluation prion
disease. The rationale for the proposed research objectives is that the β-thiolactone and β-lactone
release of cyclic ester strain enables unprecedented rapid amide bond construction and connects
two amino acid residues. Furthermore, the near-planar geometry of the cyclobutene ring will
generate desired peptidyl adducts without epimerization by preventing the oxazolone formation.
An analogous approach could be applied to construct homogenous membrane glycoproteins from
β-thiolactone promoted protein ligation. We plan to test our central hypothesis and, thereby,
accomplish the objectives of this application via the following goals: 1. Design and expansion of
the range of constrained esters that can be utilized for peptide synthesis without epimerization. 2.
Synthesis of homogeneous cellular prion glycoproteins and congeners. 3. Biological function and
activities investigation of prepared peptide and proteins.

## Key facts

- **NIH application ID:** 10201680
- **Project number:** 5R35GM138336-02
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT ALBANY
- **Principal Investigator:** Qiang Zhang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $365,558
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201680

## Citation

> US National Institutes of Health, RePORTER application 10201680, The chemical approach towards homogenous glycoprotein preparation and evaluation (5R35GM138336-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10201680. Licensed CC0.

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