Lipidic peptides. XII. Cellular uptake studies of a lipidic amino acid, its oligomers and highly lipophilic drug conjugates on Ehrlich ascites tumour cells

Abstract Cellular uptake of lipidic amino acid 1a , oligomers 1b-d , benzoquinolizine 2a and conjugates 2b-d was studied using Ehrlich ascites tumour cells. The lipidic amino acid methyl ester 1a and benzoquinolizine monomer conjugate 2b were taken up more readily and to a greater extent than the fully protected dipeptide 1b , tripeptide 1c , tetrapeptide 1d and conjugates 2c and 2d . The cellular uptake of lipophilic benzoquinolizine conjugate 2b was 5–10-fold higher than that of the unconjugated alkaloid 2a . These experiments demonstrated that conjugation with lipophilic α-amino acids could increase the cellular uptake of otherwise poorly absorbed compounds.