The synthesis of libraries of conformationally constrained peptide-like oligomers is an important goal in combinatorial chemistry. In this regard an attractive building block is the N-alkylated ...peptide, also known as a peptide tertiary amide (PTA). PTAs are conformationally constrained because of allylic 1,3 strain interactions. We report here an improved synthesis of these species on solid supports through the use of reductive amination chemistry using amino acid-terminated, bead-displayed oligomers and diverse aldehydes. The utility of this chemistry is demonstrated by the synthesis of a library of 10 000 mixed peptoid-PTA oligomers.
To understand readiness measures taken by oncologists to protect patients and health care workers from the novel coronavirus (COVID-19) and how their clinical decision making was influenced by the ...pandemic.
An online survey was conducted between March 24 and April 29, 2020.
A total of 343 oncologists from 28 countries participated. The median age was 43 years (range, 29-68 years), and the majority were male (62%). At the time of the survey, nearly all participants self-reported an outbreak in their country (99.7%). Personal protective equipment was available to all participants, of which surgical mask was the most common (n = 308; 90%). Telemedicine, in the form of phone or video encounters, was common and implemented by 80% (n = 273). Testing patients with cancer for COVID-19 via reverse transcriptase polymerase chain reaction before systemic treatment was not routinely implemented: 58% reported no routine testing, 39% performed testing in selected patients, and 3% performed systematic testing in all patients. The most significant factors influencing an oncologist's decision making regarding choice of systemic therapy included patient age and comorbidities (81% and 92%, respectively). Although hormonal treatments and tyrosine kinase inhibitors were considered to be relatively safe, cytotoxic chemotherapy and immune therapies were perceived as being less safe or unsafe by participants. The vast majority of participants stated that during the pandemic they would use less chemotherapy, immune checkpoint inhibitors, and steroids. Although treatment in neoadjuvant, adjuvant, and first-line metastatic disease was less affected, most of the participants stated that they would be more hesitant to recommend second- or third-line therapies in metastatic disease.
Decision making by oncologists has been significantly influenced by the ongoing COVID-19 pandemic.
A major goal in understanding autoimmune diseases is to define the antigens that elicit a self-destructive immune response, but this is a difficult endeavor. In an effort to discover autoantigens ...associated with type 1 diabetes (T1D), we used epitope surrogate technology that screens combinatorial libraries of synthetic molecules for compounds that could recognize disease-linked autoantibodies and enrich them from serum. Autoantibodies from one patient revealed a highly phosphorylated form of peripherin, a neuroendocrine filament protein, as a candidate T1D antigen. Peripherin antibodies were detected in 72% of donor patient sera. Further analysis revealed that the T1D-associated antibodies only recognized a dimeric conformation of peripherin. These data explain why peripherin was dismissed as an important T1D antigen previously. The discovery of this novel autoantigen would not have been possible using standard methods, such as hybridizing serum antibodies to recombinant protein arrays, highlighting the power of epitope surrogate technology for probing the mechanism of autoimmune diseases.
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•Chemical “epitope surrogates” are selective affinity probes for T1D-related IgG•Affinity-purified antibodies bind to the neuroendocrine protein, peripherin•Serum antibodies from T1D patients recognize dimeric peripherin•Phosphorylation of peripherin is critical for T1D antibody recognition
Characterizing the autoantigens that trigger adaptive immune responses is challenging, especially when epitopes are non-linear or post-translationally modified. Using “epitope surrogate” small molecules to purify disease-linked antibodies from serum, Doran et al. demonstrate that phosphorylated peripherin is a major autoantigen in patients with type 1 diabetes.
The speed and spread of the COVID-19 pandemic has been affecting the entire world for the past several months.
is a social media network made up of more than 140 oncology stakeholders: oncologists ...(medical, radiation, and surgical), oncology nurses, and patient advocates who share the mission of fighting cancer by means of education and dissemination of information. As a response to the COVID-19 pandemic, OncoAlert hosted
We have documented this effort along with further discussion about the COVID-19 pandemic and the consequences on patients living with cancer to disseminate this information to our colleagues worldwide.
In a solvent-free phase-vanishing reaction with PTFE (polytetrafluoroethylene, Teflon®) tape as the phase screen, a thermometer adapter is utilized to insert a PTFE-sealed tube into the vapor phase ...above the substrate. Besides avoiding use of solvents, the experimental design is not dependent upon the densities of the reactants and the procedure generates little or no waste while providing the reaction products in high yield and in high purity.
We demonstrate that the Knoevenagel condensation can be exploited in combinatorial synthesis on the solid phase. Condensation products from such reactions were structurally characterized, and their ...Michael reactivity with thiol and phosphine nucleophiles is described. Cyanoacrylamides were previously reported to react reversibly with thiols, and notably, we show that dilution into low pH buffer can trap covalent adducts, which are isolable via chromatography. Finally, we synthesized both traditional and DNA-encoded one-bead, one-compound libraries containing cyanoacrylamides as a source of cysteine-reactive reversibly covalent protein ligands.
The 5th Kidney Cancer Research Summit was a hybrid event hosted in Boston, MA in July 2023. As in previous editions, the conference attracted a wide representation of global thought leaders in kidney ...cancer spanning all stages of clinical and laboratory research. Sessions covered tumor metabolism, novel immune pathways, advances in clinical trials and immunotherapy, and progress toward biomarkers. The abstract presentations were published as a supplement in The Oncologist (https://academic.oup.com/oncolo/issue/28/Supplement_1). Aiming to be more concise than comprehensive, this commentary summarizes the most important emerging areas of kidney cancer research discussed and debated among the stakeholders at the conference, with relevant updates that have occurred since.
Abstract
Kidney cancer is one of the 10 most common cancers both in the United States and worldwide. Until this year, there had not previously been a conference focused on translational studies in ...the broad and heterogeneous group of kidney cancers. Therefore, a group of researchers, clinicians, and patient advocates dedicated to renal cell carcinoma launched the Kidney Cancer Research Summit (KCRS) to spur collaboration and further therapeutic advances in these tumors. This commentary aims to summarize the oral presentations and serve as a record for future iterations of this meeting. The KCRS sessions addressed the tumor microenvironment, novel methods of drug delivery, single cell sequencing strategies, novel immune checkpoint blockade and cellular therapies, predictive biomarkers, and rare variants of kidney cancers. In addition, the meeting included 2 sessions to promote scientific mentoring and kidney cancer research collaborations. A subsequent KCRS will be planned for the fall of 2020.
The second Kidney Cancer Research Summit was held virtually in October 2020. The meeting gathered worldwide experts in the field of kidney cancer, including basic, translational, and clinical ...scientists as well as patient advocates. Novel studies were presented, addressing areas of unmet need related to different topics. These include novel metabolic targets, promising immunotherapeutic regimens, predictive genomic and transcriptomic biomarkers, and variant histologies of renal cell carcinoma (RCC). With the development of pioneering technologies, and an unprecedented commitment to kidney cancer research, the field has tremendously evolved. This perspective aims to summarize the different sessions of the conference, outline major advances in the understanding of RCC and discuss current challenges faced by the field.
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