Lipidic conjugates of luteinizing hormone releasing hormone (LHRH)+ and thyrotropin releasing hormone (TRH)+ that release and protect the native hormones in homogenates of human intestinal epithelial (Caco-2) cells

Active immunisation of mice with GnRH lipopeptide vaccine candidates: Importance of T helper or multi-dimer GnRH epitope

“…26 The free amine of 2-aminohexadecanoic acid was then Boc-protected by reaction with di-tert-butyl dicarbonate in a basic environment as previously reported. 26,43 C12 was prepared to afford the pure product in 54.0% yield (1. 44 2-Aminohexadecanoic acid was synthesised as described in the literature with 1-bromotetradecane and diethyl acetoamidomalonate.…”

Modern lipid‐, carbohydrate‐, and peptide‐based delivery systems for peptide, vaccine, and gene products

“…It has been demonstrated that the conjugation of LHRH, with one or two lipoamino acids, increased the half-life of the peptide in an homogenate of human intestinal epithelial cells by approximately 30-fold (from only 2-5 min to 1-3 hr). 29 An interesting observation was made in this work: the LAA-glutamic acid bond cleaved first in a Caco-2 cell homogenate releasing the parent hormone, so by serendipity by adding LAA to the N-terminal of the LHRH, an ideal prodrug type linkage was created. 29 Conjugates with higher lipophilicity (addition of two lipoamino acids) resulted in a higher oral uptake than the conjugate with lower lipophilicity (addition of one lipoamino acid).…”

“…29 An interesting observation was made in this work: the LAA-glutamic acid bond cleaved first in a Caco-2 cell homogenate releasing the parent hormone, so by serendipity by adding LAA to the N-terminal of the LHRH, an ideal prodrug type linkage was created. 29 Conjugates with higher lipophilicity (addition of two lipoamino acids) resulted in a higher oral uptake than the conjugate with lower lipophilicity (addition of one lipoamino acid). Addition of a sugar or incorporation of LHRH into the poly-lysine system (Fig.…”

Synthesis and in vitro evaluation of a library of modified endomorphin 1 peptides

“…There is evidence, however, that the diasteriomers of Laa conjugated peptides can behave differently in vivo, particularly in terms of their stability to enzymatic degradation. 24,27,28 One of the more promising Laa conjugates in this study was therefore synthesized enantiomerically pure and both diastereomers (3 and 4) assessed individually.…”

“…We have previously shown that the incorporation of Laas into short peptides can increase their metabolic stability and passive diffusion across biological barriers. [23][24][25][26] For the majority of the analogues synthesized in this study, the lipoamino acids were introduced as a racemic mixture of both the L-and Dstereoisomers. There is evidence, however, that the diasteriomers of Laa conjugated peptides can behave differently in vivo, particularly in terms of their stability to enzymatic degradation.…”