Document Detail

N-acylated alpha-amino acids as novel oral delivery agents for proteins.
MedLine Citation:
PMID:  7473553     Owner:  NLM     Status:  MEDLINE    
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.
A Leone-Bay; N Santiago; D Achan; K Chaudhary; F DeMorin; L Falzarano; S Haas; S Kalbag; D Kaplan; H Leipold
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  38     ISSN:  0022-2623     ISO Abbreviation:  J. Med. Chem.     Publication Date:  1995 Oct 
Date Detail:
Created Date:  1995-11-28     Completed Date:  1995-11-28     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  4263-9     Citation Subset:  IM    
Emisphere Technologies, Inc., Hawthorne, New York 10532, USA.
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MeSH Terms
Amino Acids / chemistry*
Calcitonin / administration & dosage*
Calcium / blood
Drug Carriers*
Enzyme Inhibitors
Glycine / adverse effects,  analogs & derivatives*,  chemical synthesis,  pharmacology
Interferon-alpha / administration & dosage*
Intestines / anatomy & histology,  drug effects
Leucine / adverse effects,  analogs & derivatives*,  chemical synthesis,  pharmacology
Leucyl Aminopeptidase / antagonists & inhibitors
Macaca mulatta
Rats, Sprague-Dawley
Structure-Activity Relationship
Trypsin / metabolism
Trypsin Inhibitors
Reg. No./Substance:
0/Amino Acids; 0/Drug Carriers; 0/Enzyme Inhibitors; 0/Interferon-alpha; 0/Trypsin Inhibitors; 121428-84-0/N-cyclohexanoylleucine; 28172-57-8/N-cyclohexanoyl-2-phenylglycine; 47931-85-1/salmon calcitonin; 56-40-6/Glycine; 61-90-5/Leucine; 7440-70-2/Calcium; 9007-12-9/Calcitonin; EC Aminopeptidase; EC

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