PMID- 3156994
OWN - NLM
STAT- MEDLINE
DCOM- 19850510
LR  - 20190709
IS  - 0022-2623 (Print)
IS  - 0022-2623 (Linking)
VI  - 28
IP  - 4
DP  - 1985 Apr
TI  - Conjugation of poly(styrene-co-maleic acid) derivatives to the antitumor protein 
      neocarzinostatin: pronounced improvements in pharmacological properties.
PG  - 455-61
AB  - An anticancer agent of intermediate molecular weight and having both a 
      hydrophilic and hydrophobic nature was developed by utilizing the antitumor 
      protein neocarzinostatin (NCS; Mr = 12000) as a prototype drug. The modification 
      was achieved by reacting the two amino groups on NCS with an anhydride group of 
      partially half-esterified (p-E-) or partially hydrolyzed (p-H-) 
      poly(styrene-co-maleic anhydride) (SMA) in 0.8 M NaHCO3. The SMA samples with 
      narrow molecular weights distributions (Mw = ca. 2000) were prepared by 
      copolymerizing styrene and maleic anhydride in cumene followed by fractionation 
      by means of a column-elution method. The derivatives p-E- or p-H-SMA were then 
      formed by using the appropriate monoalcohols or H2O, respectively. These SMA 
      derivatives contain about 2 mol of anhydride residues/mol of SMA. The reaction 
      product, SMA-conjugated NCS (designated as SMANCS), was purified by dialysis 
      followed by gel filtration with Sephadex G-75. The complete reaction yielded 
      essentially a single product, biantennary SMANCS. The molecular weight of the 
      pure SMAMCS was estimated by various methods, including polyacrylamide gel 
      electrophoresis with NaDodSO4, HPLC in the gel permeation mode, fluorescence 
      polarization, and a decrease in both nitrogen and protein contents. These results 
      agree with the apparent molecular weight of about 16000. Characters of SMANCS was 
      considerably altered from that of parental NCS: solubility characteristics in 
      both organic and aqueous solvents were changed, the biological half-life in blood 
      was prolonged 10 times, and antitumor activity became more pronounced, but the 
      toxicity was reduced to one-fourth of the parental NCS. Thus, the present study 
      has provided a method of improving biologically active substances by polymer 
      conjugation.
FAU - Maeda, H
AU  - Maeda H
FAU - Ueda, M
AU  - Ueda M
FAU - Morinaga, T
AU  - Morinaga T
FAU - Matsumoto, T
AU  - Matsumoto T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 9014-02-2 (Zinostatin)
SB  - IM
MH  - Animals
MH  - *Antibiotics, Antineoplastic/*chemical synthesis/pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Molecular Weight
MH  - Structure-Activity Relationship
MH  - Zinostatin/*analogs & derivatives
EDAT- 1985/04/01 00:00
MHDA- 1985/04/01 00:01
CRDT- 1985/04/01 00:00
PHST- 1985/04/01 00:00 [pubmed]
PHST- 1985/04/01 00:01 [medline]
PHST- 1985/04/01 00:00 [entrez]
AID - 10.1021/jm00382a012 [doi]
PST - ppublish
SO  - J Med Chem. 1985 Apr;28(4):455-61. doi: 10.1021/jm00382a012.