Abstract: Protein structural determination using NMR techniques is improved through use of proteins in which one or more amino acids in the peptidic sequence are isotopically enriched in the sidechain with 2H and are isotopically enriched on the backbone with 13C, 15N, 2H or any combination thereof. This invention provides amino acids isotopically enriched as above, which can be used to synthesize isotopically labeled proteins and peptides for protein structural determinations by NMR, and methods for their synthesis. Other embodiments of the invention include peptidic molecules, media for peptidic molecule expression, methods of making isotopically labeled peptidic molecules and methods of determining structural information of a peptidic molecule.
Type:
Application
Filed:
March 15, 2011
Publication date:
December 22, 2011
Applicant:
ProSpect Pharma
Inventors:
Jonathan Miles Brown, Steven W. Homans, Michael Chaykovsky, Jenny Hong Murray
Abstract: Protein structural determination using NMR techniques is improved through use of proteins in which one or more amino acids in the peptidic sequence are isotopically enriched in the sidechain with 2H and are isotopically enriched on the backbone with 13C, 15N, 2H or any combination thereof. This invention provides amino acids isotopically enriched as above, which can be used to synthesize isotopically labeled proteins and peptides for protein structural determinations by NMR, and methods for their synthesis. Other embodiments of the invention include peptidic molecules, media for peptidic molecule expression, methods of making isotopically labeled peptidic molecules and methods of determining structural information of a peptidic molecule.
Type:
Application
Filed:
October 7, 2004
Publication date:
November 29, 2007
Applicant:
ProSpect Pharma
Inventors:
Jonathan Brown, Steven Homans, Michael Chaykovsky, Jenny Murray
Abstract: This invention provides an NMR method for obtaining both entropic and enthalpic data on proteins and protein/ligand complexes which can be used to obtain accurate structural and dynamic data of proteins and protein complexes having a wide range of molecular weights. An embodiment of the invention provides proteins which contain at least one bond vector whose dynamics are to be measured and which is surrounded by NMR inactive nuclei, and amino acids for synthesis of the proteins via chemical means or biological expression. The NMR methods using specifically labeled proteins for analysis result in maximization of the sensitivity and resolution of the NMR experiments, and minimization of the loss of signal due to diffusion.
Type:
Application
Filed:
June 10, 2003
Publication date:
July 13, 2006
Applicant:
ProSpect Pharma
Inventors:
Jonathan Brown, Steven Homans, Minn-Chang Cheng, Michael Chaykovsky, Jenny Murray
Abstract: This invention provides a method for rapidly obtaining accurate three-dimensional structure of proteins including large or multi-sub unit proteins, using a combination of NMR analysis of backbone only 13C, 15N or 13C and 15N isotopically labeled proteins which are optionally also 2H isotopically labeled in the C? position protons and residual dipolar coupling measurements in more than one partially aligned state and/or orientation data pertaining to overlapping successive peptide pairs.