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Anionic inhibitors of pancreatic and leukocyte elastase. Alkylamides of 3-carboxypropionyl- and 4-carboxybutyrylalanine peptides. 1985

E Kasafírek, and P Fric, and J Slabý

Low-molecular inhibitors of pancreatic and leukocyte elastase were synthesized of the general formula X-[Ala]n-A [X = Suc and Glt, A = ethylamide, n = 1, 2, 3 and 4; for n = 2 X = H and A = (2-phenylethyl)amide] and of the formula X-[Ala]3-A (X = H, Suc and Glt, A = methyl-, ethyl-, propyl-, isopropyl-, butyl-, isobutyl-, (2-phenylethyl)- and diethylamide; for A = ethylamide, X = maleyl or acetyl). Inhibition constants Ki of these pancreatic and leukocyte elastase inhibitors were determined using the chromogenic substrates Suc-[Ala]4-Nan or Glt-[Ala]4-Nan and Glt-[Ala]3-Val-Nan, respectively. The series of anionic inhibitors containing three alanine residues has the best inhibitory properties. Of the acyl groups, 4-carboxybutyryl appears most advantageous, propylamide is the most suitable of alkylamides for pancreatic elastase, and isobutylamide for leukocyte elastase. Peptides containing a free amino group show an inhibition for pancreatic elastase lower by one order than that of the corresponding acylated derivatives. Glt-[Ala]3-NH-Pr is the best inhibitor of pancreatic elastase with Ki = 0.003mM and Suc-[Ala]3-NH-iBu is the best inhibitor of leukocyte elastase with Ki = 0.7mM.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D007962 Leukocytes White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES). Blood Cells, White,Blood Corpuscles, White,White Blood Cells,White Blood Corpuscles,Blood Cell, White,Blood Corpuscle, White,Corpuscle, White Blood,Corpuscles, White Blood,Leukocyte,White Blood Cell,White Blood Corpuscle
D009842 Oligopeptides Peptides composed of between two and twelve amino acids. Oligopeptide
D010179 Pancreas A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
D010196 Pancreatic Elastase A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25,000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. EC 3.4.21.36. Elastase,Pancreatopeptidase,Elastase I,Pancreatic Elastase I,Elastase I, Pancreatic,Elastase, Pancreatic
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
D013379 Substrate Specificity A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts. Specificities, Substrate,Specificity, Substrate,Substrate Specificities
D013552 Swine Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA). Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D066298 In Vitro Techniques Methods to study reactions or processes taking place in an artificial environment outside the living organism. In Vitro Test,In Vitro Testing,In Vitro Tests,In Vitro as Topic,In Vitro,In Vitro Technique,In Vitro Testings,Technique, In Vitro,Techniques, In Vitro,Test, In Vitro,Testing, In Vitro,Testings, In Vitro,Tests, In Vitro,Vitro Testing, In

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