About

Sidney M. Hecht is the director for the Center for BioEnergetics in the Biodesign Institute at Arizona State University. He researches diseases caused by defects in the body's energy production processes. Energy production is similar mechanistically to other molecular processes that he has studied extensively. He played a key role in the development of Hycamtin, a drug used to treat ovarian and lung cancer, as well as the study of the mechanism of the anti-tumor agent bleomycin. In a career spanning more than three decades, Professor Hecht has held both academic and industrial research positions. He joins ASU from the University of Virginia, where he was a professor of both chemistry and biology. From 1981 to 1987, he concurrently held leadership positions in research and development for Smith Kline and French Laboratories. Prior to his 28 years at the University of Virginia, he was a faculty member at MIT. Hecht is the co-founder of Edison Pharmaceuticals, a pharmaceutical company focusing on inherited mitochondrial disorders. He earned a B.A. in chemistry from the University of Rochester and a Ph.D. in chemistry with emphasis in biochemistry from the University of Illinois.

Research topics

• Biochemistry
• Biology
• Chemistry
• Pharmacology
• Medicine
• Pathology
• Neuroscience

Selected publications

• Enzyme-free, femtomolar detection of dengue virus RNA via hierarchical quantum dot signal amplification and toehold-mediated strand displacement

  Microchemical Journal · 2026-05-01

  article
  PublisherDOI

• Enzyme-Free, Femtomolar Detection of Dengue Virus RNA via Hierarchical Quantum Dot Signal Amplification and Toehold-Mediated Strand Displacement

  SSRN Electronic Journal · 2026-01-01

  preprintOpen access
  PublisherDOI

• A Quantum Dot–Based Platform for Room-Temperature Detection of Dengue Virus RNA

  Preprints.org · 2026-01-01

  preprintOpen access

  Dengue viruses continue to pose a significant global public health challenge, especially in tropical and subtropical regions where access to centralized laboratory infrastructure is often limited. Prompt identification of dengue virus RNA during the early, acute phase of infection is essential for effective clinical management and timely outbreak response. However, widely used gold-standard techniques such as reverse transcription–polymerase chain reaction (RT-PCR) rely on enzymatic amplification, advanced instru-mentation, and skilled personnel, which restricts their use in point-of-care and re-source-constrained settings. In this work, an enzyme-free nucleic acid detection strategy based on semiconductor quantum dots (Qdots) is described for sensitive and specific dengue virus RNA detection at room temperature. The platform combines toe-hold-mediated strand displacement reactions (TMDRs) for precise sequence recognition with the strong fluorescence and signal amplification capabilities of Qdots. A highly con-served sequence at the 3′ end of the dengue genome was selected to enable detection across all four viral serotypes. Viral RNA is captured by surface-immobilized probes via TMDR, followed by binding Qdot-labeled detection probes and a Qdot-driven signal amplification step, all under isothermal conditions. The assay demonstrated femtomolar sensitivity us-ing synthetic RNA targets and maintained high performance in crude nucleic acid ex-tracts from contrived samples representing all dengue serotypes. Its modular, enzyme-free design offers a simple, rapid, and highly sensitive alternative to conventional amplifica-tion-based diagnostics, with strong potential for low-cost, portable applications in molec-ular diagnostics.

  PublisherOA PDFDOI

• Alteration of CD40 Protein Expression by Tyrosine Phosphorylation of the NF‐ <i>κ</i> B p50 Subunit

  ChemBioChem · 2025-11-26 · 1 citations

  articleOpen accessSenior authorCorresponding

  Protein phosphorylation is critical to selective gene expression; the proteins that regulate transcription are often phosphorylated at multiple sites. Serine and threonine phosphorylation in transcription factors such as NF-κB has been studied, and specific serines are involved in transcriptional activation. Tyrosine phosphorylation of NF-κB p50 subunit can also facilitate the NF-κB-mediated expression of CD40 protein. This study seeks to determine whether tyrosine phosphorylations at positions not normally phosphorylated in vivo could nonetheless affect protein expression mediated by NF-κB. The alterations studied included p50 analogs having pTyr at positions 59 and 61, which do not contain Tyr naturally, and an analog containing a metabolically stable tyrosine methylene phosphonate at position 60. Additionally, to explore the structural basis for enhanced NF-κB binding to CD40 promoter DNA by tyrosine phosphorylation, an analog of NF-κB p50 containing pTyr at both positions 60 and 82 is prepared. The results reflected changes in the ability of the modified NF-κBs containing an altered p50 subunit to bind to CD40 promoter DNA in vitro, and to direct the synthesis of CD40 in cellulo.

  PublisherOA PDFDOI

• Biological Regulation Studied <i>in Vitro</i> and <i>in Cellulo</i> with Modified Proteins

  Accounts of Chemical Research · 2025-03-12

  articleOpen accessSenior authorCorresponding

  ConspectusProteins and peptides occur ubiquitously in organisms and play key functional roles, as structural elements and catalysts. Their major natural source is ribosomal synthesis, which produces polypeptides from 20 amino acid building blocks. Peptides containing noncanonical amino acids have long been prepared by chemical synthesis, which has provided a wealth of physiologically active compounds. Comparatively, preparing modified proteins has been more challenging. Site-directed mutagenesis provided an important advance but was initially limited to canonical amino acids. New techniques for tRNA activation with noncanonical amino acids subsequently increased the scope of site-directed mutagenesis.Our report in 2012 demonstrated that modification of bacterial ribosomes at key positions enabled the selection of ribosomes capable of introducing β-amino acids into proteins in vitro. The generality of the selection procedure was tested further. Ribosomes capable of incorporating dipeptides, conformationally constrained dipeptides, dipeptidometics with embedded fluorophores, contiguous nucleobase amino acids, and phosphorylated amino acids were successfully identified.In this Account, we focus on the application of the new technology to dramatically alter protein structure in ways that enable new strategies for understanding and altering protein function. To illustrate the robustness of the technology we have provided examples studied in vitro and in cellulo. The first category involves the introduction of nucleobase amino acids into proteins in support of specific interactions with RNA and DNA. The energetic differences between potential protein–nucleic acid complexes formed from two binding partners are often quite small. It seems logical to think that selective binding can be achieved by using a nucleobase moiety in each of the binding partners by utilizing known interactions between nucleic acid bases (located in the protein and nucleic acid) to achieve energetically favorable interactions. We do so both in vitro and in cellulo. A second focus has involved the design of small fluorescent probes not much larger than amino acids that are genetically encodable and which can be incorporated during protein biosynthesis, serving as detectable probes of protein trafficking and interaction with other macromolecules. We provide an in vitro example of strongly fluorescent tryptophan analogues positioned at single sites within dihydrofolate reductase, permitting selective communication with a FRET acceptor at a known position, even in the presence of several tryptophans. An oxazole amino acid, weakly fluorescent in aqueous solution, fluoresced more strongly following incorporation into MreB, a scaffold protein produced in cellulo. Finally, we describe the introduction of a single phosphorylated tyrosine into the p50 subunit of NF-κB. When present at either of two key positions, the resulting NF-κB significantly enhanced binding in vitro to the promoter DNA as well as subsequent mRNA transcription of its client protein CD40 in cellulo. In a separate expression in activated Jurkat cells, an increased production of CD40 protein was observed.

  PublisherOA PDFDOI

• Functionalized Nitrobenzothiadiazoles as Embedded Fluorescent Probes

  The Journal of Organic Chemistry · 2025-06-25

  articleOpen accessSenior authorCorresponding

  Described herein is the synthesis and photophysical characterization of novel dipeptidomimetic fluorogenic probes. The new dipeptidomimetic cassette is based on the environment-sensitive fluorophore nitrobenzothiadiazole (NBTD) and is designed to be embedded within a polypeptide backbone, not attached as part of a conformationally unrestrained amino acid side chain. Compounds 1–6 were prepared to investigate the effect of introducing a methyl group at positions 5 and 6 of the nitrobenzothiadiazole scaffold on their photophysical properties. Additionally, we investigated the effect of N-methylation of the 4-amino group on their chemical and photophysical properties. The nitrobenzothiadiazole scaffold was functionalized with amino- and carboxy-termini, resulting in a conformationally restricted dipeptidomimetic scaffold (NBTD-Gly) that can potentially be embedded within peptides or proteins of interest and used as a biophysical tool for studying protein structure and function. Thus, we investigated the synthesis and photophysical properties of functionalized nitrobenzothiadiazoles (1–11). The amino-terminus of the dipeptidomimetic scaffold (NBTD-Gly) was introduced at the benzylic position of the benzothiadiazole core using Gabriel synthesis, followed by nitration. The carboxy terminus was introduced via nucleophilic aromatic substitution as part of the glycine moiety. Subsequent steps involved the removal of a phthaloyl protecting group and a condensation reaction to form protected dipeptidomimetic analogues 7–11.

  PublisherOA PDFDOI

• Enhancement of <i>N</i>-Methyl Amino Acid Incorporation into Proteins and Peptides Using Modified Bacterial Ribosomes and Elongation Factor P

  ACS Chemical Biology · 2024-05-20 · 7 citations

  articleSenior authorCorresponding

  N-Methylated amino acids are constituents of natural bioactive peptides and proteins. Nα-methylated amino acids appear abundantly in natural cyclic peptides, likely due to their constraint of peptide conformation and contribution to peptide stability. Peptides containing Nα-methylated amino acids have long been prepared by chemical synthesis. While such natural peptides are not produced ribosomally, recent ribosomal strategies have afforded Nα-methylated peptides. Presently, we define new strategies for the ribosomal incorporation of Nα-methylated amino acids into peptides and proteins. First, we identify modified ribosomes capable of facilitating the incorporation of six N-methylated amino acids into antibacterial scorpion peptide IsCT. Also synthesized analogously was a protein domain (RRM1) from hnRNP LL; improved yields were observed for nearly all tested N-methylated amino acids. Computational modeling of the ribosomal assembly illustrated how the distortion imposed by N-methylation could be compensated by altering the nucleotides in key 23S rRNA positions. Finally, it is known that incorporation of multiple prolines (an N-alkylated amino acid) ribosomally can be facilitated by bacterial elongation factor P. We report that supplementing endogenous EF-P during IsCT peptide and RRM1 protein synthesis gave improved yields for most of the N-methylated amino acids studied.

  PublisherDOI

• Opportunities and challenges for innovative and equitable healthcare

  Nature Reviews Drug Discovery · 2024-02-26 · 8 citations

  review
  PublisherDOI

• Supplementary Data from Identification of the First Specific Inhibitor of p90 Ribosomal S6 Kinase (RSK) Reveals an Unexpected Role for RSK in Cancer Cell Proliferation

  2023-03-30

  preprintOpen access

  &lt;p&gt;Supplementary text, 3 figures, and 1 table.&lt;/p&gt;

  PublisherDOI

• Supplementary Data from Identification of the First Specific Inhibitor of p90 Ribosomal S6 Kinase (RSK) Reveals an Unexpected Role for RSK in Cancer Cell Proliferation

  2023-03-30

  preprintOpen access

  &lt;p&gt;Supplementary text, 3 figures, and 1 table.&lt;/p&gt;

  PublisherOA PDFDOI

Recent grants

• NIH Grant U01CA050771

  NIH · $2.6M · 1995

• NIH Grant R01CA077359

  NIH · $2.9M · 2008

• NIH Grant R01CA077284

  NIH · $2.1M · 2008

• Dynamic Properties that Enhance Enzyme Function

  NIH · $1.3M · 2010–2015

• NIH Grant R01GM027815

  NIH · $251k · 1987

Frequent coauthors

• Shengxi Chen

  Arizona State University

  100 shared

• Omar M. Khdour

  Arizona State University

  92 shared

• Larisa M. Dedkova

  Arizona State University

  75 shared

• Craig J. Thomas

  48 shared

• David G. I. Kingston

  Virginia Tech

  46 shared

• Christian Bailly

  Onco Lille

  42 shared

• Randall K. Johnson

  Mississippi College

  41 shared

• Brian M. Eisenhauer

  University of Virginia

  40 shared

Education

• Ph.D., Chemistry (minor Biochemistry)

  University of Illinois

  1970

• B.A., Chemistry

  University of Rochester

  1966