Biomaterial Database

Toward new designed proteins derived from bovine pancreatic trypsin inhibitor (BPTI): covalent cross-linking of two 'core modules' by oxime-forming ligation. 2001

N Carulla, and C Woodward, and G Barany

Department of Chemistry, University of Minnesota, Minneapolis, Minnesota 55455, USA.

A 25-residue disulfide-cross-linked peptide, termed 'oxidized core module' (OxCM), that includes essentially all of the secondary structural elements of bovine pancreatic trypsin inhibitor (BPTI) most refractory to hydrogen exchange, was shown previously to favor nativelike beta-sheet structure [Carulla, N., Woodward, C., and Barany, G. (2000) Synthesis and Characterization of a beta-Hairpin Peptide That Represents a 'Core Module' of Bovine Pancreatic Trypsin Inhibitor (BPTI). Biochemistry 39, 7927-7937]. The present work prepares to explore the hypothesis that the energies of nativelike conformations, relative to other possible conformations, could be decreased further by covalent linkage of two OxCMs. Optimized syntheses of six approximately 50-residue OxCM dimers are reported herein, featuring appropriate monomer modifications followed by oxime-forming ligation chemistry to create covalent cross-links at various positions and with differing lengths. Several side reactions were recognized through this work, and modified procedures to lessen or mitigate their occurrence were developed. Particularly noteworthy, guanidine or urea denaturants that were included as peptide-solubilizing components for some reaction mixtures were proven to form adducts with glyoxylyl moieties, thus affecting rates and outcomes. All six synthetic OxCM dimers were characterized by 1D (1)H NMR; three of them showed considerable chemical shift dispersion suggestive of self-association and mutual stabilization between the monomer units.

UI	MeSH Term	Description	Entries
D007611	Aprotinin	A single-chain polypeptide derived from bovine tissues consisting of 58 amino-acid residues. It is an inhibitor of proteolytic enzymes including CHYMOTRYPSIN; KALLIKREIN; PLASMIN; and TRYPSIN. It is used in the treatment of HEMORRHAGE associated with raised plasma concentrations of plasmin. It is also used to reduce blood loss and transfusion requirements in patients at high risk of major blood loss during and following open heart surgery with EXTRACORPOREAL CIRCULATION. (Reynolds JEF(Ed): Martindale: The Extra Pharmacopoeia (electronic version). Micromedex, Inc, Englewood, CO, 1995)	BPTI, Basic Pancreatic Trypsin Inhibitor,Basic Pancreatic Trypsin Inhibitor,Bovine Kunitz Pancreatic Trypsin Inhibitor,Kallikrein-Trypsin Inactivator,Kunitz Pancreatic Trypsin Inhibitor,Trypsin Inhibitor, Basic, Pancreatic,Trypsin Inhibitor, Kunitz, Pancreatic,Antilysin,Bovine Pancreatic Trypsin Inhibitor,Contrical,Contrykal,Dilmintal,Iniprol,Kontrikal,Kontrykal,Pulmin,Traskolan,Trasylol,Zymofren,Inactivator, Kallikrein-Trypsin,Kallikrein Trypsin Inactivator
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D008969	Molecular Sequence Data	Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.	Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D009682	Magnetic Resonance Spectroscopy	Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).	In Vivo NMR Spectroscopy,MR Spectroscopy,Magnetic Resonance,NMR Spectroscopy,NMR Spectroscopy, In Vivo,Nuclear Magnetic Resonance,Spectroscopy, Magnetic Resonance,Spectroscopy, NMR,Spectroscopy, Nuclear Magnetic Resonance,Magnetic Resonance Spectroscopies,Magnetic Resonance, Nuclear,NMR Spectroscopies,Resonance Spectroscopy, Magnetic,Resonance, Magnetic,Resonance, Nuclear Magnetic,Spectroscopies, NMR,Spectroscopy, MR
D010091	Oximes	Compounds that contain the radical R2C	Aldoximes,Hydroxyimino Compounds,Ketoxime,Ketoximes,Oxime,Compounds, Hydroxyimino
D010455	Peptides	Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.	Peptide,Polypeptide,Polypeptides
D002417	Cattle	Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.	Beef Cow,Bos grunniens,Bos indicus,Bos indicus Cattle,Bos taurus,Cow,Cow, Domestic,Dairy Cow,Holstein Cow,Indicine Cattle,Taurine Cattle,Taurus Cattle,Yak,Zebu,Beef Cows,Bos indicus Cattles,Cattle, Bos indicus,Cattle, Indicine,Cattle, Taurine,Cattle, Taurus,Cattles, Bos indicus,Cattles, Indicine,Cattles, Taurine,Cattles, Taurus,Cow, Beef,Cow, Dairy,Cow, Holstein,Cows,Dairy Cows,Domestic Cow,Domestic Cows,Indicine Cattles,Taurine Cattles,Taurus Cattles,Yaks,Zebus
D003432	Cross-Linking Reagents	Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other.	Bifunctional Reagent,Bifunctional Reagents,Cross Linking Reagent,Crosslinking Reagent,Cross Linking Reagents,Crosslinking Reagents,Linking Reagent, Cross,Linking Reagents, Cross,Reagent, Bifunctional,Reagent, Cross Linking,Reagent, Crosslinking,Reagents, Bifunctional,Reagents, Cross Linking,Reagents, Cross-Linking,Reagents, Crosslinking
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia