Nα-Fmoc-L-lysine allyl ester hydrochloride

Spurred by significant progress in materials chemistry and drug delivery, charge-reversal nanocarriers are being developed to deliver anticancer formulations in spatial-, temporal- and dosage-controlled approaches. Charge-reversal nanoparticles can release their drug payload in response to specific stimuli that alter the charge on their surface. They can elude clearance from the circulation and be activated by protonation, enzymatic cleavage, or a molecular conformational change. In this review, we discuss the physiological basis for, and recent advances in the design of charge-reversal nanoparticles that are able to control drug biodistribution in response to specific stimuli, endogenous factors (changes in pH, redox gradients, or enzyme concentration) or exogenous factors (light or thermos-stimulation).

A simple and practical synthesis of the benzyl, allyl, and 4-nitrobenzyl esters of N-[2-(Fmoc)aminoethyl]glycine is described starting from the known N-(2-aminoethyl)glycine. These esters are stored as stable hydrochloride salts and were used in the synthesis of peptide nucleic acid monomers possessing bis-N-Boc-protected nucleobase moieties on the exocyclic amino groups of ethyl cytosin-1-ylacetate, ethyl adenin-9-ylacetate and ethyl (O(6)-benzylguanin-9-yl)acetate. Upon ester hydrolysis, the corresponding nucleobase acetic acids were coupled to N-[2-(Fmoc)aminoethyl]glycine benzyl ester or to N-[2-(Fmoc)aminoethyl]glycine allyl ester in order to retain the O(6) benzyl ether protecting group of guanine. The Fmoc/bis-N-Boc-protected monomers were successfully used in the Fmoc-mediated solid-phase peptide synthesis of mixed sequence 10-mer PNA oligomers and are shown to be a viable alternative to the currently most widely used Fmoc/Bhoc-protected peptide nucleic acid monomers.

A series of dopamine agonists were studied on contraversive circling behavior in seven 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced hemiparkinsonian monkeys. The compounds selected included [1R,3S]3-(1' adamantyl)-1-aminomethyl-3,4-dihydro-5-6- dihydroxy-1H-2-benzopyran hydrochloride (A-77636), L-3,4-dihydroxyphenylalanine methyl ester hydrochloride ester (L-dopa-methyl ester), (-)-2-[N-propyl-N-(2-thienyl) ethyl-amino-5-hydroxy-tetralin]hydrochloride (N-0923), pergolide, (+)-(4aR)-trans-3,4,4a,5,6,10b-hexahydro-4-propyl-2H-n aphth[1,2-b]-1,2-oxazin-9-ol, naxagolide (PHNO), (+/-)6-chloro-7, 8-dihydroxy-2,3,4,5-tetrahydro-1-phenyl-1H-3-benzazepine hydrobromide, (+-) chloro-PB hydrobromide (SKF-81297) and (+-) 6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benza zep ine hydrobromide, (+-) chloro-APB hydrobromide (SKF-82958). The dose-effect relationship of each of these compounds was determined by measuring contraversive turns/120 min after an i.m. injection. There were marked differences in the potency and efficacy of the various compounds studied. The most potent compounds were the selective D2 agonists PHNO and N-0923. L-dopa methyl ester was equally effective, but much less potent. The D1 agonist A-77636 was equally effective. The D1 agonist SKF-82958 was also effective, but less potent. In the doses studied, the D1 agonist SKF-81297 was ineffective. With the exception of L-dopa methyl ester, the greater the D1/D2 affinity ratio, the greater the 50% of maximal dose to induce contraversive circling (r = 0.974, P < .05).