Peptide Knowledge Center

Research Progress of Glycine Derivatives

Glycine derivatives are used in many aspects such as industry, agriculture and medicine(very common used amino acid derivatives). It is used as an effective chelating agent for metal ions in industry; it is used as pesticides, herbicides, plant growth regulators, etc. in agriculture; the application of glycine derivatives in medicine is a relatively active research field in recent years, such as Glycine derivatives can enhance the efficacy of thiamphenicol and β-lactam antibiotics, as well as intermediates for the synthesis of anti-tumor drugs.

Glycine, also known as aminoacetic acid, has a molecular formula of NH2CH2COOH. As early as 1820, Braquenau isolated glycine from gelatin. Because it is a crystal with a special sweet taste, it is called gum. In 1848, the Swedish chemist Berzelius named it glycine. Glycine is a white crystal or crystalline powder with a sweet taste. It has a melting point of 232~236 ℃ (decomposition). It is soluble in water, insoluble in ethanol and ether. It can react with hydrochloric acid to form hydrochloride, which is present in the muscles of lower animals. Glycine has a wide range of uses. It is one of the essential amino acids for the human body. Glycine is basically contained in various amino acid infusion formulas; it can also be used as a flavoring and additive for food. Adding glycine to food can increase the amino acid in food. In addition, glycine has a unique effect as an antioxidant and preservative in food.

Glycine is one of more than 20 common amino acids involved in protein composition. It is the only amino acid that does not contain chiral carbon atoms, so it is not optically active. Due to the special structure of glycine, it has an irreplaceable role in the field of new drug synthesis and biochemistry research. Glycine derivative medicines have the characteristics of rich sources, low prices, small side effects, and wide applications.

Application of Glycine Derivatives in Medicine

Glycine derivatives have important medicinal value and development prospects, such as

1. Glycine derivatives can enhance the efficacy of thiamphenicol

Thiamphenicol (thiamphenicol), thiamphenicol is a synthetic broad-spectrum antibiotic, mainly related to inhibiting protein synthesis and inhibiting antibody production. Thiamphenicol has low toxicity, but due to its poor water solubility, its application in dosage forms and clinical applications is limited.

Thiamphenicol glycinate hydrochloride has good water solubility. Basic pharmacological studies have shown that the drug can be used as a prodrug of thiamphenicol and can be made into various preparations (such as injections, granules, oral liquids). Etc.), after enzymatic hydrolysis in the body, thiamphenicol is quickly released and then exerts pharmacological effects.

Thiamphenicol glycinate hydrochloride is synthesized by condensation, hydrolysis, and salt formation with thiamphenicol with glycine as a raw material under the protection of amino groups.

2. Improve the efficacy of β-lactam antibiotics

Beta-lactam antibiotics are the most widely used and effective antibacterial drugs. With the long-term use of these antibiotics, bacteria have developed strong resistance to them. The N-acetyl derivative of the higher alcohol ester of glycine can be used as a synergist of penicillin, increasing the antibacterial performance of penicillin by 4 times, and Relieve the pain of the patient when using it.

3. Intermediates for the synthesis of anti-tumor drugs

3-Pyrrolidone hydrochloride is an important intermediate for the synthesis of natural anti-tumor drug camptothecin (cmnp-tothecin). Using glycine, N-(2-acetonitrile) glycine, ethyl glycinate, and ethyl N-ethoxycarbonylglycinate as starting materials respectively, 3-pyrrolidone hydrochloride can be synthesized

4. Synthesize bradykinin antagonists, angiotensin antagonists, luteinizing hormone antagonists, renin antagonists, protease inhibitors and other biologically active substance antagonists.

Bradykinin is a peptide (8 amino acids) substance produced after kininogen is hydrolyzed by vasomotor hormone in the body, which can promote smooth muscle contraction and vasodilation, regulate blood flow speed or participate in inflammatory response. Bradykinin also has the effects of lowering blood pressure, increasing membrane permeability, and causing pain.; Solid-phase peptide synthesis technology is used to synthesize bradykinin structural analogs (8 peptides).

Angiotensin hydrolyzes certain globulins in plasma to produce angiotensin. Angiotensin has the effect of stimulating capillary contraction and raising blood pressure. Angiotensin antagonists can inhibit the activity of angiotensin-converting enzyme and reduce angiotensin., Use solid-phase peptide synthesis technology to synthesize peptides (9 peptides), in which 1, 2 or 3 amino acids in the peptide are replaced by N-benzylglycine or The reduction product N-cyclohexylmethylglycine is substituted. These synthetic peptides are also angiotensin antagonists, and angiotensin antagonists can be used to treat hypertension.

A biologically active peptide synthesized by solid-phase peptide synthesis technology. The antagonist constructed by replacing 1, 2 or 3 amino acids in the peptide with N-benzylglycine or its reduction product N-cyclohexylmethylglycine also has a luteinizing hormone antagonist. (11 peptides), can be used for the treatment of breast cancer (depletion of luteinizing hormone); renin antagonists (10 peptides), can inhibit renin production and lower blood pressure.

Proteases are hydrolytic enzymes whose role is to catalyze the decomposition of proteins in the body. For example, elastin is hydrolyzed by elastase, and elastin exists in arteries, ligaments, lungs, etc. Human lung elastin is about 28%. HLE inhibitors synthesized by glycine derivatives have good application prospects in the diagnosis and treatment of emphysema, rheumatoid arthritis, osteoarthritis, arteriosclerosis and other diseases. With the improvement of living standards and the acceleration of the pace of life, the number of people suffering from modern diseases such as hypertension has increased.Glycine derivatives and their substituted peptide drugs are more effective for these modern diseases.