Andrij Buchynskyy

Studies on the interaction of the antibiotic moenomycin A with the enzyme penicillin-binding protein 1b

The interaction of a moenomycin derivative with the enzyme penicillin binding protein 1b (PBP 1b) has been studied by means of STD NMR. The results obtained initiated the synthesis of a number of moenomycin derivatives modified in unit A including a moenomycin-ampicillin conjugate and determination of their antibiotic activities. A protocol is described that allows studying the interaction of moenomycin analogues with PBP 1b by fluorescence correlation spectroscopy.

Some selective reactions of moenomycin A.

A number of new moenomycin A derivatives have been prepared. Their antibiotic properties highlight the very specific recognition of moenomycin A at the transglycosylase binding site which is the basis of the transglycosylase inhibiting property of moenomycin A (4a).

Membrane Anchoring and Intervesicle Transfer of a Derivative of the Antibiotic Moenomycin A.

The anchoring of moenomycin A (1) to the bacterial cell cytoplasmic membrane is essential for its biological activity. The first details of the strength of this interaction and the kinetics of the diffusion-mediated intervesicle transfer have been obtained by means of fluorescence spectroscopic methods using a coumarin-labeled moenomycin A derivative.

Moenomycin‐Mediated Affinity Purification of Penicillin‐Binding Protein 1b

The antibiotic moenomycin A inhibits the biosynthesis of peptidoglycan, the main structural polymer of the bacterial cell wall. The inhibition is based on a reversible binding of the antibiotic to one of the substrate binding sites at enzymes such as the penicillin binding protein 1b (PBP 1b). This binding has been employed to isolate PBP 1b by affinity chromatography. Suitable ligands have been prepared from moenomycin A and coupled both to affinity supports and to surface plasmon resonance sensor surfaces. The reactions that take place upon immobilization of the ligands to the affinity support and the sensor surface, respectively, have been studied in detail. With the help of surface plasmon resonance the optimal conditions for binding of PBP 1b to moenomycin‐derivated ligands have been established. For the first time the selective binding of the moenomycin sugar moiety to the enzyme has been demonstrated.

Synthesis of fluorescent derivatives of the antibiotic moenomycin A.

Moenomycin has been highly selectively converted into amino derivative 3b. The primary amino group of this compound can be used to attach various fluorescent labels to moenomycin, through conversion of isothiocyanates into thioureas and squaric acid diesters into diamides. The application of some of the derivatives is outlined. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Synthesis of tools for raising antibodies against moenomycin epitopes and initial immunological studies

Abstract The moenomycins A and C 1 as well as penta-, di- and monosaccharide analogues have been conjugated to BSA and biotin, respectively. The moenomycin A–BSA conjugates have been used to raise polyclonal antibodies. It has been demonstrated that the antisera recognize moenomycin A.

A Method for the Introduction of Reporter Groups into Moenomycin A, Based on Thiouronium Salt Chemistry

p-Alkoxy-substituted cinnamylthiouronium salts 7, 13, 21a, and 21b reacted selectively with the 2-acylamino-1,3-cyclopentanedione unit A of moenomycin A (1) to give the corresponding 2-alkylated products 14a, 14b, 22a, and 22b. These products, depending on the pH of the solution, were either stable under the reaction conditions or they underwent retro-Claisen-type reactions. The method can be used for the attachment of reporter groups to moenomycin A for the synthesis of, for example, 25. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)