Biomaterial Database

Nasal mucosal metabolism and absorption of pentapeptide enkephalin analogs having varying N-terminal amino acids. 1995

M A Hussain, and R Seetharam, and R R Wilk, and B J Aungst, and C A Kettner

DuPont Merck Pharmaceutical Company, Wilmington, DE 19880-0400.

A series of enkephalin analogs with varying amino acids on the N-terminus were synthesized and evaluated in rats in situ for their hydrolytic stability and absorption when administered nasally. The amino acids on the N-terminus were tyrosine (Y), alanine (A), serine (S), lysine (K), and aspartic acid (D). These amino acids represent different charges and sizes. Among these peptides, only the peptide carrying aspartic acid on the N-terminus was stable. The rank order of degradation rates was YGGFL > AGGFL > SGGFL, KGGFL > DGGFL. These results suggest that there are relatively high activities of aminopeptidases N and B and relatively low activity of aminopeptidase A in the rat nasal mucosa. Absorption studies were performed to determine the absorption rate of DGGFL, by measuring percentage recovery of nasal doses vs time. After a 50 microL dose of a 3 mg/mL solution, this peptide exhibited an absorption half-life of 21 min, which is similar to the nasal absorption rate of YGGFL.

UI	MeSH Term	Description	Entries
D008297	Male		Males
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
D009297	Nasal Mucosa	The mucous lining of the NASAL CAVITY, including lining of the nostril (vestibule) and the OLFACTORY MUCOSA. Nasal mucosa consists of ciliated cells, GOBLET CELLS, brush cells, small granule cells, basal cells (STEM CELLS) and glands containing both mucous and serous cells.	Nasal Epithelium,Schneiderian Membrane,Epithelium, Nasal,Membrane, Schneiderian,Mucosa, Nasal
D002851	Chromatography, High Pressure Liquid	Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.	Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D004745	Enkephalins	One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla.	Enkephalin
D006207	Half-Life	The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity.	Halflife,Half Life,Half-Lifes,Halflifes
D006868	Hydrolysis	The process of cleaving a chemical compound by the addition of a molecule of water.
D000042	Absorption	The physical or physiological processes by which substances, tissue, cells, etc. take up or take in other substances or energy.
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