Recent developments in the cleavage, functionalization, and conjugation of proteins and peptides at tyrosine residues

Brimble, Margaret A.; Zhang, Shengping; Rodriguez, Luis Manuel M De Leon; Li, Freda F.

doi:10.1039/d3sc02543h

Cited by 13 publications

(5 citation statements)

References 150 publications

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“…This particular result based on the BEF analysis may be quite useful in virtual fragmentation processes, more precisely when defining the bond in which fragmentation should occur without altering the basic electronic structure of the original molecule. Fragmentation processes are very useful in many different situations such as cleavage of proteins and peptides 12 or the partitioning of molecular electron density into atomic or groups components to learn more about reactivity or to perform calculations in large molecular systems. 59 Carrying out the BEF analysis to rationally decide which bond is more prone to produce the molecular fragmentation could lead to interesting results.…”

Section: Application To Diatomics and Few Simple Symmetric Moleculesmentioning

confidence: 99%

“…The LEF analysis can also be useful in many other situations such as the selective modification of proteins and peptides through bond-cleavage processes. In this context, the a priori identification of bonds that could be more easily scissed 12 can be facilitated by the LEF analysis, which recognize the backbone's bonds that are more pronned to be cleaved; the criterion for cleavage being opposite to that for reactivity: low electronic activity. The LEF analysis provides then a nonarbitrary criterion to rationally produce molecular fragmentation by identifying the electronically less active bonds, which would be more likely to be virtually cleaved.…”

Section: Introductionmentioning

confidence: 99%

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Basis Electronic Activity of Molecular Systems. A Theory of Bond Reactivity

Benítez,

Gutiérrez-Oliva,

Herrera

et al. 2024

J. Phys. Chem. A

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In this paper, we present a new finding, the basis electronic activity (BEA) of molecular systems; it corresponds to the significant, although nonreactive, vibrationally induced electronic activity that takes place in any molecular system. Although the molecule's BEA is composed of an equal number of local contributions as the vibrational degrees of freedom, our results indicate that only stretching modes contribute to it. To account for this electronic activity, a new descriptor, the bond electronic flux (BEF), is introduced. The BEF combined with the force constant of the potential well hosting the electronic activity gives rise to the effective bond reactivity index (EBR), which turns out to be the first density functional theory-based descriptor that simultaneously accounts for structural and electronic effects. Besides quantifying the bond reactivity, EBR provides a basis to compare the reactivities of bonds inserted in different chemical environments and paves the way for the exertion of selective control to enhance or inhibit their reactivities. The new concepts formulated in this paper and the associated computational tools are illustrated with characterization of the BEA of a set of representative molecules. In all cases, the BEFs follow the same linear pattern, whose slopes indicate the intensity of the electronic activity and quantify the reactivity of chemical bonds.

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Section: Application To Diatomics and Few Simple Symmetric Moleculesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Basis Electronic Activity of Molecular Systems. A Theory of Bond Reactivity

Benítez,

Gutiérrez-Oliva,

Herrera

et al. 2024

J. Phys. Chem. A

View full text Add to dashboard Cite

show abstract

“…Finally, through the addition of cDNA that is fully complementary to HD22 for aptamer removal purposes, a protein-RO conjugate can be successfully obtained. In addition, there are many selective modifications based on peptides and protein sites that can also be used as hot spots for future CALI technology research and development [75][76][77]. It is believed that in the near future, with the continuous development of protein site-selective modification and aptamers, CALI can be achieved in any protein.…”

Section: Future Perspective Of Calimentioning

confidence: 99%

Chromophore-Assisted Light Inactivation for Protein Degradation and Its Application in Biomedicine

Zhou,

Na,

Liu

et al. 2024

Bioengineering

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The functional investigation of proteins holds immense significance in unraveling physiological and pathological mechanisms of organisms as well as advancing the development of novel pharmaceuticals in biomedicine. However, the study of cellular protein function using conventional genetic manipulation methods may yield unpredictable outcomes and erroneous conclusions. Therefore, precise modulation of protein activity within cells holds immense significance in the realm of biomedical research. Chromophore-assisted light inactivation (CALI) is a technique that labels photosensitizers onto target proteins and induces the production of reactive oxygen species through light control to achieve precise inactivation of target proteins. Based on the type and characteristics of photosensitizers, different excitation light sources and labeling methods are selected. For instance, KillerRed forms a fusion protein with the target protein through genetic engineering for labeling and inactivates the target protein via light activation. CALI is presently predominantly employed in diverse biomedical domains encompassing investigations into protein functionality and interaction, intercellular signal transduction research, as well as cancer exploration and therapy. With the continuous advancement of CALI technology, it is anticipated to emerge as a formidable instrument in the realm of life sciences, yielding more captivating outcomes for fundamental life sciences and precise disease diagnosis and treatment.

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“…[3] To this end, Cys is the most widely targeted residue in proteins owing to its relatively high nucleophilicity under physiological conditions. [4] Therefore, many efforts have been made over the past few years by researchers worldwide and resulted in strategies that could access other nucleophilic residues in proteins, such as Lys, [5] Tyr, [6] Trp, [7] His [8] and Met. [9] Review papers on the relevant topics have been elegantly written.…”

Section: Introductionmentioning

confidence: 99%

Pinpointing Acidic Residues in Proteins

Xuan,

2024

ChemMedChem

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It is of great importance to pinpoint specific residues or sites of a protein in biological contexts to enable desired mechanism of action for small molecules or to precisely control protein function. In this regard, acidic residues including aspartic acid (Asp) and glutamic acid (Glu) hold great potential due to their great prevalence and unique function. To unlock the largely untapped potential, great efforts have been made recently by synthetic chemists, chemical biologists and pharmacologists. Herein, we would like to highlight the remarkable progress and particularly introduce the electrophiles that exhibit reactivity to carboxylic acids, the light‐induced reactivities to carboxylic acids and the genetically encoded noncanonical amino acids that allow protein manipulations at acidic residues. We also comment on certain unresolved challenges, hoping to draw more attention to this rapidly developing area.

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Recent developments in the cleavage, functionalization, and conjugation of proteins and peptides at tyrosine residues

Abstract: Peptide and protein selective modification at tyrosine residues has become an exploding field of research as tyrosine constitutes a robust alternative to lysine and cysteine-targeted traditional peptide/protein modification protocols. This...

Cited by 13 publications

References 150 publications

Basis Electronic Activity of Molecular Systems. A Theory of Bond Reactivity

Basis Electronic Activity of Molecular Systems. A Theory of Bond Reactivity

Chromophore-Assisted Light Inactivation for Protein Degradation and Its Application in Biomedicine

Pinpointing Acidic Residues in Proteins

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