Biomaterial Database

Synthesis and dopamine receptor modulating activity of lactam conformationally constrained analogues of Pro-Leu-Gly-NH2. 1993

U Sreenivasan, and R K Mishra, and R L Johnson

Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis 55455.

A series of analogues of the potent analogue of Pro-Leu-Gly-NH2 (PLG), 2-oxo-3(R)-[(2(S)-pyrrolidinylcarbonyl)amino]-1-pyrrolidineacet amide (2) were synthesized in which the (R)-gamma-lactam residue of 2 was replaced with a (R)-beta-lactam, (R)-aminosuccinimide, (R)-cycloseryl, (R)-delta-lactam, (R)-epsilon-lactam, or (S)-epsilon-lactam residue to give analogues 3-8, respectively. These substitutions were made so as to vary the psi 2 torsion angle. The analogues were tested for their ability to enhance the binding of the dopamine receptor agonist ADTN to the dopamine receptor. Analogues 3-6 and 8 exhibited dose-response curves that were bell-shaped in nature with the maximum effect occurring at a concentration of 1 microM. Analogue 7 was inactive. Analogues 3 and 4 were found to be as effective as PLG, while analogues 5, 6, and 8 appeared to be more effective than PLG in terms of enhancing the binding of ADTN to dopamine receptors. The activity of analogues 3-6 and 8 with their psi 2 angles in the vicinity of that observed in a type II beta-turn is consistent with the hypothesis that this type of turn is the bioactive conformation of PLG.

UI	MeSH Term	Description	Entries
D007769	Lactams	Cyclic AMIDES formed from aminocarboxylic acids by the elimination of water. Lactims are the enol forms of lactams.	Lactam,Lactim,Lactims
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
D009842	Oligopeptides	Peptides composed of between two and twelve amino acids.	Oligopeptide
D011954	Receptors, Dopamine	Cell-surface proteins that bind dopamine with high affinity and trigger intracellular changes influencing the behavior of cells.	Dopamine Receptors,Dopamine Receptor,Receptor, Dopamine
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
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
D013329	Structure-Activity Relationship	The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.	Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013764	Tetrahydronaphthalenes	Partially saturated 1,2,3,4-tetrahydronaphthalene compounds.	Tetralins
D015259	Dopamine Agents	Any drugs that are used for their effects on dopamine receptors, on the life cycle of dopamine, or on the survival of dopaminergic neurons.	Dopamine Drugs,Dopamine Effect,Dopamine Effects,Dopaminergic Agents,Dopaminergic Drugs,Dopaminergic Effect,Dopaminergic Effects,Agents, Dopamine,Agents, Dopaminergic,Drugs, Dopamine,Drugs, Dopaminergic,Effect, Dopamine,Effect, Dopaminergic,Effects, Dopamine,Effects, Dopaminergic