Solid-phase synthesis of deglycobleomycins: A C-terminal tetraamine linker that permits direct evaluation of resin-bound bleomycins

Zhi Fu Tao, Christopher J. Leitheiser, Kenneth L. Smith, Shigeki Hashimoto, Sidney M. Hecht

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Deglycobleomycin analogues having different length polyamine side chains at the C-terminus were synthesized using a novel solid-phase synthesis strategy that produces fully deprotected deglycobleomycin congeners attached to the resin. Detailed studies of DNA cleavage by these compounds and their resin-bound counterparts using supercoiled plasmid DNAs and DNA restriction fragments as substrates revealed that (i) the length of the polyamine side chain of free deglycoBLM had limited effect on its DNA cleavage potency or sequence selectivity, and (ii) the nature of the linker moiety between the resin and attached deglycobleomycin had a more substantial effect on the potency of DNA cleavage, but no effect on sequence selectivity of resin-bound deglycoBLMs. Resin-bound 4 exhibited efficient DNA cleavage, indicating that its tetraamine linker moiety could be used for the elaboration and direct evaluation of bleomycin congeners attached to resins.

Original languageEnglish (US)
Pages (from-to)426-434
Number of pages9
JournalBioconjugate chemistry
Volume13
Issue number3
DOIs
StatePublished - 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

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