A new method for chemoselective conjugation of unprotected peptides to dauno- and doxorubicin

Bioorganic and Medicinal Chemistry Letters

Volumn 11, Issue 10, 2001, Pages 1343-1346

  Ingallinella, Paolo ^a   Di Marco, Annalise ^a   Taliani, Marina ^a   Fattori, Daniela ^a   Pessi, Antonello ^a  

^a IRBM   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

DAUNORUBICIN; DAUNORUBICIN DERIVATIVE; DOXORUBICIN; DOXORUBICIN DERIVATIVE; OXIME;

ARTICLE; DRUG CONJUGATION; DRUG STRUCTURE; DRUG SYNTHESIS; ISOMER; LIGATION; PH; REACTION ANALYSIS; STEREOCHEMISTRY;

AMINO ACID SEQUENCE; ANTINEOPLASTIC AGENTS; DAUNORUBICIN; DOXORUBICIN; DRUG DELIVERY SYSTEMS; HYDROGEN-ION CONCENTRATION; MOLECULAR SEQUENCE DATA; PEPTIDES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0035927243     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(01)00223-2     Document Type: Article

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11. +] m/z 640.
12. 2O) over 20 min, UV detection at 214 and 490 nm).
13. 1H NMR chemical shift upon oxime formation. The ratio between regioisomers was calculated by integration of the area of the respective HPLC peak (detection: UV, 214 nm).
14. +] m/z 656.
15. +] m/z 3643, calcd 3642.
16. +] m/z 3643, calcd 3642.
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20. The test peptide derivative 4b was used to further analyze the specific oxime linkage present in our derivatives with respect to ex vivo stability and toxicity: (a) 4b was incubated with human plasma, and no traces of the starting ketone 2b were detected after 2.5 h (analysis by LC-MS); (b) 4b was incubated with Jurkat cells up to a concentration of 100 μmol, without observing any significant toxicity.