토끼의 수종 점막 추출액중 로이신엔케팔린 및 [D-알라2]-로이신엔케팔린아미드의 효소적 분해 특성

• 영문명: Enzymatic Degradation of Leucine Enkephalin and [D-Ala2]-Leucine Enkephalinamide in Various Rabbit Mucosa Extracts
• 발행기관: 대한약학회
• 저자명: 전인구(In Koo Chun) 박인숙(In Sook Park)
• 간행물 정보: 『약학회지』제38권 제5호 (1994년), 530~543쪽, 전체 14쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 1994.10.30

영문 초록

To study the feasibility of transmucosal delivery of leucine enkephalin (Leu-Enk) and [D-ala2]-leucine enkephalinamide (YAGFL), their degradation extents and pathways in various rabbit mucosa extracts were investigated by high performance liquid chromatography. The degradation of Leu-Enk and YAGFL was observed to follow the first-order kinetics. The degradation half-lives of Leu-Enk in the nasal, rectal and vaginal mucosal extracts were 1.62, 0.37 and 1.12 hrs and those of YAGFL were 30.55, 9.70 and 6.82 hrs, respectively, indicating Leu-Enk was degraded in a more extensive and rapid manner than YAGFL. But the mucosal and serosal extracts of the same mucosa showed the similar degradation rates for both pentapeptides. The degradation was most rapid in the neutral pH and increasing concentrations of substrates retarded the degradation rates. The major hydrolytic fragments of Leu-Enk were Des-Tyr-Leu-Enk and tyrosine, indicating the enzymatic hydrolysis by aminopeptidases. However, the data also suggested endopeptidases such as dipeptidyl carboxypeptidase and dipeptidyl aminopeptidase could play some role in the degradation of Leu-Enk. On the other hand, the hydrolytic fragments of YAGFL in all the mucosa extracts were mainly Tyr-D-Ala-Gly and Phe-Leu-Amide, demonstrating the hydrolytic breakdown by endopeptidases. The degradation pathways were further explored by concomitantly determining the formation of smaller metabolites of primary hydrolytic fragments of Leu-Enk and YAGFL in the mucosa extracts.

키워드

Leucine enkephalin [D-Ala2]-Ieucine enkephalinamide nasal rectal and vaginal mucosa extracts enzymatic degradation degradation pathway.