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Chemical modifications for improveme...

Pooyan, Shahriar.

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Chemical modifications for improvement of the pharmacological properties of therapeutic agents.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Chemical modifications for improvement of the pharmacological properties of therapeutic agents./
Author:	Pooyan, Shahriar.
Description:	177 p.
Notes:	Source: Dissertation Abstracts International, Volume: 64-09, Section: B, page: 4385.
Contained By:	Dissertation Abstracts International64-09B.
Subject:	Chemistry, Polymer. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3105565

Chemical modifications for improvement of the pharmacological properties of therapeutic agents.
Pooyan, Shahriar.

Chemical modifications for improvement of the pharmacological properties of therapeutic agents. - 177 p.

Source: Dissertation Abstracts International, Volume: 64-09, Section: B, page: 4385.

Thesis (Ph.D.)--Rutgers The State University of New Jersey - New Brunswick and University of Medicine and Dentistry of New Jersey, 2003.

N-Formyl-methionyl peptides can specifically bind to surface receptors on phagocytic cells. A single copy of N-formyl-methionine-leucine-phenylalanine (fMLF) covalently linked to a poly(ethylene glycol)-based polymer displayed reduced binding avidity (Kd = 190 nM) for differentiated HL-60 cells relative to free fMLF (Kd = 28 nM). However, increasing the number of fMLF residues (up to eight) attached to a single polymer resulted in enhanced avidity for these cells (Kd = 0.18 nM). However, no conjugates showed enhanced ability to activate phagocytic cells, relative to free peptide (EC50 = 5 nM), as measured by transient stimulation of released calcium ions from intracellular stores into the cytoplasm. A polymer bearing four fMLF and four digoxigenin residues showed specific enhancement in binding to differentiated HL-60 cells and mouse peritoneal macrophages in situ relative to a polymer lacking fMLF. These results suggest that multiple fMLF residues linked to a drug-delivery polymer can be used to target appended drugs to phagocytic cells with relatively low toxicity due to cellular activation.Subjects--Topical Terms:

1018428
Chemistry, Polymer.

Chemical modifications for improvement of the pharmacological properties of therapeutic agents.
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100 1 $a Pooyan, Shahriar. $3 1948991
245 1 0 $a Chemical modifications for improvement of the pharmacological properties of therapeutic agents.
300 $a 177 p.
500 $a Source: Dissertation Abstracts International, Volume: 64-09, Section: B, page: 4385.
500 $a Director: Stanley Stein.
502 $a Thesis (Ph.D.)--Rutgers The State University of New Jersey - New Brunswick and University of Medicine and Dentistry of New Jersey, 2003.
520 $a N-Formyl-methionyl peptides can specifically bind to surface receptors on phagocytic cells. A single copy of N-formyl-methionine-leucine-phenylalanine (fMLF) covalently linked to a poly(ethylene glycol)-based polymer displayed reduced binding avidity (Kd = 190 nM) for differentiated HL-60 cells relative to free fMLF (Kd = 28 nM). However, increasing the number of fMLF residues (up to eight) attached to a single polymer resulted in enhanced avidity for these cells (Kd = 0.18 nM). However, no conjugates showed enhanced ability to activate phagocytic cells, relative to free peptide (EC50 = 5 nM), as measured by transient stimulation of released calcium ions from intracellular stores into the cytoplasm. A polymer bearing four fMLF and four digoxigenin residues showed specific enhancement in binding to differentiated HL-60 cells and mouse peritoneal macrophages in situ relative to a polymer lacking fMLF. These results suggest that multiple fMLF residues linked to a drug-delivery polymer can be used to target appended drugs to phagocytic cells with relatively low toxicity due to cellular activation.
520 $a A unique feature of the HIV-1 replication cycle is its requirement for the virally encoded Tat protein to bind to a region in nascent viral transcripts (TAR) and alleviate a transcriptional blockage. Previously, in our laboratory, a Tat peptide antagonist [N-acetyl-RKKRRQRRRK(biotin)-NH2] was designed based on the TAR binding domain of Tat peptide (Wang et al., 1995). In this study, this Tat antagonist was synthesized with D-amino acids, assembled in reverse order of that found in parent peptide (commonly referred to as retro-inverso peptide). The retro-inverso antagonist peptide appended to PEG showed an inhibitory effect in HIV-1 replication at 0.01 muM concentration. Also, bioreversible PEG polymers, that could serve as carriers for peptides or proteins, were synthesized and characterized in this study.
520 $a A polycation peptide-antisense DNA conjugate was synthesized in order to study the effect of positive charges on the neutralization of negative charges on the oligonucleotide moiety. A competitive gel shift assay was designed to determine the dissociation constant of this oligonucleotide conjugate. This modification resulted in a three-fold increase of binding affinity to the single-stranded DNA or RNA targets.
590 $a School code: 0801.
650 4 $a Chemistry, Polymer. $3 1018428
650 4 $a Biology, Microbiology. $3 1017734
650 4 $a Chemistry, Pharmaceutical. $3 550957
690 $a 0495
690 $a 0410
690 $a 0491
710 2 0 $a Rutgers The State University of New Jersey - New Brunswick and University of Medicine and Dentistry of New Jersey. $3 1023857
773 0 $t Dissertation Abstracts International $g 64-09B.
790 1 0 $a Stein, Stanley, $e advisor
790 $a 0801
791 $a Ph.D.
792 $a 2003
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3105565