Collagen is the most abundant protein in humans, comprising 1/3 of the total protein and 3/4 of the dry weight of skin. Collagen abnormalities are associated with many human diseases, including arthritis. The overall objective of the proposed research is to extend the fundamental understanding of the structure and stability of the collagen triple helix that we have acquired during the previous grant period and to create collagen mimetics and conjugates of potential utility for clinical indications.
Specific Aims : The three Specific Aims of this research proposal apply methods and ideas from physical organic chemistry, peptide chemistry, biophysics, microbiology, matrix biology, and dermatology.
Aim 1 employs a newly appreciated force?the n-to-?* interaction?and other physicochemical interactions to generate an optimal collagen mimetic peptide (CMP) for annealing tightly but noncovalently to damaged collagen.
Aim 2 uses CMP conjugates to probe the collagen displayed on the surface of a pathogenic bacterium, Streptococcus pyrogenes, and to antagonize its infectivity. Finally, Aim 3 uses CMP conjugates to assess burn wounds in human skin. Significance: The results of the research proposed herein will provide insights into the structure and stability of the collagen triple helix in natural contexts, and will use those insights to develop the basis for transformative molecular therapies for microbial infections and burns.

Public Health Relevance

This research project is focused on collagen, which is the most abundant protein in humans. Collagen abnormalities are associated with a variety of human diseases, including arthritis. The goal of the project is to obtain insights into the relationship between the amino acid sequence of collagen and its biological function (or dysfunction), as well as to create novel collagen-like peptides of potential clinical utility.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
High Priority, Short Term Project Award (R56)
Project #
2R56AR044276-23A1
Application #
10017536
Study Section
Synthetic and Biological Chemistry B Study Section (SBCB)
Program Officer
Tseng, Hung H
Project Start
1996-07-15
Project End
2021-08-31
Budget Start
2019-09-20
Budget End
2020-08-31
Support Year
23
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Massachusetts Institute of Technology
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02142