Amino Acid/Peptide

October 9, 2012

Site-Selective Chemistry and the Attachment of Peptides to the Surface of a Microelectrode Array

Melissae Stuart Fellet, Jennifer L. Bartels, Bo Bi, and Kevin D. Moeller

J. Am. Chem. Soc., 2012, 134 (40), pp 16891–16898

Peptides have been site-selectively placed on microelectrode arrays with the use of both thiol-based conjugate additions and Cu(I)-coupling reactions between thiols and aryl halides. The conjugate addition reactions used both acrylate and maleimide Michael acceptors. Of the two methods, the Cu(I)-coupling reactions proved far superior because of their irreversibility. Surfaces constructed with the conjugate addition chemistry were not stable at neutral pHs, especially the surface using the maleimide acceptor. Once a peptide was placed onto the array, it could be monitored in “real-time” for its interactions with a biological receptor.

 

January 20, 2012

Building Addressable Libraries: Amino Acid Derived Fluorescent Linkers

Takamasa Tanabe, Bo Bi, Libo Hu, Karl Maurer, and Kevin D. Moeller

Langmuir, 2012, 28 (3), 1689-1693

A new amino acid derived fluorescent linker for attaching molecules to the surface of a microelectrode array has been developed. Molecules to be monitored on an array are attached to the C-terminus of the linker, the N-terminus is then used to attach the linker to the array, and the side chain is used to synthesize a fluorescent tag. The fluorescent group is made with a one-step oxidative cycloaddition reaction starting from a hydroxyindole group. The linker is compatible with site-selective Cu(I)-chemistry on the array, it allows for quality control assessment of the array itself, and it is compatible with the electrochemical impedance experiments used to monitor binding events on the surface of the array.

 

October 3, 2006

Building Functionalized Peptidomimetics: Use of Electroauxiliaries for Introducing N-Acyliminium Ions into Peptides

Haizhou Sun, Connor Martin, David Kesselring, Rebecca Keller, and Kevin D. Moeller
J. Am. Chem. Soc., 2006, 128 (42), 13761–13771

A series of silyl-substituted amino acids have been synthesized, inserted into peptides, and then employed as precursors for oxidatively generating reactive N-acyliminium ions. Both electrochemical and chemical oxidation procedures have been employed. N-Acyliminium ion generation in a solid-phase substrate as well as application to a small library of functionalized dipeptides has been demonstrated. Limitations in terms of how electron-rich the silyl groups can be as well as the compatibility of multiple silyl groups within a longer peptide are defined.

 

October 20, 2003

Constrained Peptidomimetics: Building Bicyclic Analogs of Pyrazoline Derivatives

Bin Liu, John D Brandt and Kevin D Moeller
Tetrahedron, 2003, 59 (43), 8515-8523

A synthetic route has been developed for incorporating pyrazoline derivatives as proline surrogates in constrained X-Pro peptidomimetics. The route allows for the synthesis of dipeptide building blocks having either a six or seven-membered-ring annulated onto the pyrazoline moiety, as well as for the asymmetric synthesis of analogs having substituents on N-terminal side of the building block.

 

August 15, 2003

Building Functionalized Peptidomimetics: New Electroauxiliaries and the Use of a Chemical Oxidant for Introducing N-Acyliminium Ions into Peptides

Haizhou Sun and Kevin D. Moeller
Org. Lett., 2003, 5 (18), pp 3189–3192

The removal of electroauxiliaries from peptide substrates with chemical oxidants has been examined as a method for inserting N-acyliminium ions into the peptides. To this end, it was found that both 4-methoxyphenyldimethylsilyl and 2,4-dimethoxyphenyldimethylsilyl electroauxiliaries were readily cleaved with the use of ceric ammonium nitrate. Of the two groups, the 2,4-dimethoxyphenyldimethylsilyl electroauxiliary was the most labile under the oxidative conditions. The oxidation reactions were shown to be compatible with the use of a solid-phase substrate.

 

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