N-ACYLATED ALPHA-AMINO-ACIDS AS NOVEL ORAL DELIVERY AGENTS FOR PROTEINS

被引：68

作者：

LEONEBAY, A

SANTIAGO, N

ACHAN, D

CHAUDHARY, K

DEMORIN, F

FALZARANO, L

HAAS, S

KALBAG, S

KAPLAN, D

LEIPOLD, H

LERCARA, C

OTOOLE, D

RIVERA, T

ROSADO, C

SARUBBI, D

VUOCOLO, E

WANG, NF

MILSTEIN, S

BAUGHMAN, RA

机构：

[1] Emisphere Technologies, Inc., Hawthorne, New York 10532

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1995年 / 38卷 / 21期

关键词：

D O I：

10.1021/jm00021a015

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of N-acylated alpha-amino acids were synthesized and shown to improve the oral delivery of two protein drugs, salmon calcitonin (sCT) and interferon-alpha. Forty-five compounds in this series were tested in vivo in rats and primates. A significant positive correlation was found between the log P of the acylated amino acids and the decrease in serum calcium following oral dosage of sCT in rats. Such a correlation was not found for interferon-alpha. These derivatized amino acids only weakly inhibited the activity of trypsin or leucine aminopeptidase. Histological examinations of rat intestinal tissue after oral dosing of acylated amino acid/protein combinations revealed no detectable pathology.

引用

页码：4263 / 4269

页数：7

共 47 条

[11] TREATMENT AND PREVENTION OF CHRONIC VIRAL-HEPATITIS [J].

DUSHEIKO, GM .

PHARMACOLOGY & THERAPEUTICS, 1995, 65 (01) :47-73

[12]

Emisphere Technologies Inc, 1995, [No title captured], Patent No. [US5401516, 5401516]

[13] FUROSEMIDE, MITHRAMYCIN, AND SALMON CALCITONIN IN HYPERCALCEMIA [J].

FILLASTRE, JP ;

HUMBERT, G ;

LEROY, J ;

MAITROT, J ;

DESHAYES, P ;

CANONNE, MA .

EUROPEAN JOURNAL OF INTENSIVE CARE MEDICINE, 1975, 1 (04) :185-188

[14]

GREENSTEIN JP, 1962, CHEM AMINO ACIDS, V2, P1266

[15]

HAMMOND BR, 1956, BIOCHEM J, V221, P287

[16] FORMATION OF SPECIFIC AMINO-ACID-SEQUENCES DURING THERMAL POLYMERIZATION OF AMINO-ACIDS [J].

HARTMANN, J ;

BRAND, MC ;

DOSE, K .

BIOSYSTEMS, 1981, 13 (03) :141-147

[17]

HIMOE A, 1967, J BIOL CHEM, V242, P919

[18] BIOPHYSICAL MODEL APPROACHES TO MECHANISTIC TRANSEPITHELIAL STUDIES OF PEPTIDES [J].

HO, NFH ;

DAY, JS ;

BARSUHN, CL ;

BURTON, PS ;

RAUB, TJ .

JOURNAL OF CONTROLLED RELEASE, 1990, 11 (1-3) :3-24

[19] TREATMENT OF SEVERE HYPERCALCEMIA WITH CALCITONIN [J].

HOSKING, DJ .

METABOLIC BONE DISEASE & RELATED RESEARCH, 1980, 2 (03) :207-212

[20]

Humphrey M. J., 1986, DELIVERY SYSTEMS PEP, P139

← 1 2 3 4 5 →