Dock-able linear and homodetic di,tri,tetra and pentapeptide library from canonical amino acids:SARS-CoV-2 Mpro as a case study / 药物分析学报

Peptide-based therapeutics are increasingly pushing to the forefront of biomedicine with their promise of high specificity and low toxicity.Although noncanonical residues can always be used,employing only the natural 20 residues restricts the chemical space to a finite dimension allowing for comprehensive in silico screening.Towards this goal,the dataset comprising all possible di-,tri-,and tetra-peptide com-binations of the canonical residues has been previously reported.However,with increasing computa-tional power,the comprehensive set of pentapeptides is now also feasible for screening as the comprehensive set of cyclic peptides comprising four or five residues.Here,we provide both the com-plete and prefiltered libraries of all di-,tri-,tetra-,and penta-peptide sequences from 20 canonical amino acids and their homodetic(N-to-C-terminal)cyclic homologues.The FASTA,simplified molecular-input line-entry system(SMILES),and structure-data file(SDF)-three dimension(3D)libraries can be readily used for screening against protein targets.We also provide a simple method and tool for conducting identity-based filtering.Access to this dataset will accelerate small peptide screening workflows and encourage their use in drug discovery campaigns.As a case study,the developed library was screened against severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)main protease to identify po-tential small peptide inhibitors.

Manifestaciones extrarticulares y anticuerpos contra péptidos cíclicos citrulinados en artritis reumatoide / Extrarticular manifestations and antibodies against citrullinated cyclic peptides in rheumatoid arthritis

Introducción: La artritis reumatoide se manifiesta como enfermedad inflamatoria sistémica presenta manifestaciones extrarticulares. Objetivos: Determinar la frecuencia de manifestaciones extrarticulares en pacientes con artritis reumatoide, identificar las más frecuentes y su asociación con anticuerpos contra péptidos cíclicos citrulinados. Métodos: Se realizó un estudio descriptivo y transversal, en 101 pacientes con diagnóstico de artritis reumatoide, atendidos en La Consulta Protocolizada del Servicio de Reumatología del Hospital Clínico Quirúrgico Hermanos Ameijeiras, entre agosto y diciembre del año 2019. Se identificaron características sociodemográficas como edad, sexo, tiempo de evolución de la artritis reumatoide y tabaquismo. Se buscaron presencia de manifestaciones extrarticulares por el interrogatorio, examen físico y con ayuda de exámenes complementarios y se determinaron los títulos de anticuerpos contra péptidos cíclicos citrulinados en el plasma de los pacientes. Resultados: Las manifestaciones extrarticulares estuvieron presentes en 38 pacientes para 37,6 por ciento de los casos, las más frecuentes fueron los nódulos subcutáneos 37 pacientes, y la anemia en 35 que constituyen 36,6 por ciento y 34,7 por ciento de los casos, respectivamente. Fueron positivos a antipéptidos cíclicos citrulinados 78 enfermos, 77,2 por ciento de la muestra, no existió asociación entre presencia de los antipéptidos cíclicos citrulinados y la actividad de la enfermedad. No existió asociación significativa entre estos anticuerpos y las manifestaciones extrarticulares p<0,0001. Fue significativa la asociación entre los niveles de antipéptidos cíclicos citrulinados y el número de manifestaciones extrarticulares en un paciente p=0,0018. Conclusiones: Las manifestaciones articulares existentes en los pacientes estudiados se asociaron, significativamente, con la presencia de los antipéptidos cíclicos citrulinados(AU)

Introduction: Rheumatoid arthritis within its expression as a systemic inflammatory disease presents extra-articular manifestations. Objectives: To determine the frequency of extra-articular manifestations in patients with rheumatoid arthritis, to identify the most frequent and their association with antibodies against citrullinated cyclic peptides. Methods: A descriptive and cross-sectional study was carried out in 101 patients with a diagnosis of rheumatoid arthritis, assisted in the protocolized consultation of Rheumatology service at Hermanos Ameijeiras Clinical Surgical Hospital, from August to December 2019. Sociodemographic characteristics were identified, such as age, sex, time of evolution of rheumatoid arthritis, smoking habits. The presence of extra-articular manifestations was searched for by questioning, physical examination and with the help of complementary tests, and the titers of antibodies against citrullinated cyclic peptides were determined in the plasma of the patients. Results: Extra-articular manifestations were present in 38 patients, 37.6percent of the cases, the most frequent were subcutaneous nodules in 37 patients, and anemia in 35, which constituted 36.6percent and 34.7percent of the cases, respectively. Seventy eight patients were positive for citrullinated cyclic antipeptides, 77.2percent of the sample, there was no association between the presence of citrullinated cyclic antipeptides and the activity of the disease. There was no significant association between the presence of these antibodies and the presence of extra-articular manifestations p <0.0001, the association between the levels of citrullinated cyclic antipeptides and the number of extra-articular manifestations in a patient was significant p=0.0018. Conclusions: The existing joint manifestations in the studied patients were significantly associated with the presence of citrullinated cyclic antipeptides(AU)

Chemical constituent analysis for seeds of Celosia argentea by UPLC-ESI-Q-TOF-MS / 中国中药杂志

This Paper aimed to analyze and identify the chemical constituents from the seeds of Celosia argentea by UPLC-ESI-Q-TOF-MS. The analysis was performed on an ACQUITY HSS T3 reverse phase column(2.1 mm ×100 mm, 1.8 μm). The mobile phase consisting of 0.1% formic acid acetonitrile and 0.1% aqueous formic acid was used for gradient elution, and the flow rate was 0.4 mL·min~(-1). Mass spectrometry was applied for the qualitative analysis under positive and negative ionization modes and ESI ion source. Data was analyzed by Masslynx 4.1 software, literatures in SciFinder database, and standards. A total of 49 compounds, including 14 triterpenoids, 17 flavonoids, 11 cyclic peptides, 2 phenols, 2 organic acids, and 3 steroids were putatively identified. Among them, 19 compounds were firstly reported from this species. In-depth chemical constituent analysis for the seeds of C. argentea were accomplished here, and the findings could lay a good foundation for its quality control and clarifying the material basis of its efficacy.

Desarrollo de un péptido cíclico marcado con 99mTc dirigido contra el receptor de la vitronectina / Development of a 99mTc-labeled cyclic peptide with affinity for the vitronectine receptor

El objetivo del presente trabajo fue desarrollar un péptido híbrido, que presente una secuencia capaz de quelatar al 99mTc y otra con afinidad por el receptor de la vitronectina, que permita la detección in vivo de tumores malignos. El marcaje del péptido PICIC3 con 99mTc se realizó de forma directa. Se estudió la estabilidad del complejo en exceso de L-cisteína y en plasma, la unión a proteínas plasmáticas, el coeficiente de partición en el sistema NaCl 0.9 por ciento:n-octanol, la carga del complejo mediante electroforesis y la afinidad por el receptor de la vitronectina se valoró a partir de un ensayo de saturación con membranas de células B16-F10. Se determinó la biodistribución en ratones C57BL/6 con injertos de melanoma B16-F10. Conclusiones: El péptido desarrollado mostró una afinidad satisfactoria por el receptor de la vitronectina y que permitió la detección in vivo de los melanomas múridos del tipo B16-F10 en los ratones injertados.

The aim of the present work was to develop a hybrid peptide, with a sequence for the chelation of 99mTc and other with affinity for the vitronectine receptor, to allow in vivo detection of malignant tumors. 99mTc-labeling of peptide PICIC3 was directly performed. The stability in presence of L-cysteine excess and plasma of the complex, its binding to plasma proteins, the partition coefficient in NaCl 0.9 percent:n-octanol, the charge of the chelate by electrophoresis and the peptide affinity for the vitronectine receptor by a saturation assay using membranes of B16-F10 cells, were studied. Biodistribution in C57BL/6 mice injerted with melanoma B16-F10 was assessed. Conclusions: Developed peptide showed a satisfactory affinity for the vitronectine receptor and allowed in vivo detection of murine melanomas in mice with allografts.

Standard dimensions for cis N-methyl peptide unit and flexibility of cis peptide units.

The mean dimensions of the cis N-methyl peptide unit have been arrived at by analysing the crystal structure data on compounds containing such units. These dimensions can be used as standard in conformational studies on cyclic peptides. While the bonds meeting at C are almost coplanar, those meeting at Ν show a slight pyramidal disposition. A comparison of the dimensions of the normal and N-methylated cis peptide units show that there are perceptible differences in the parameters connected with N. In addition, the flexibility of the cis peptide unit has been analysed by studying the distribution of the parameters in different classes of compounds such as cyclic di, tri and higher peptides. The salient features are: (i) The angle CαCN in cyclic dipeptide and the angle CδNCα in higher peptides tend to be lower, when the peptide unit is associated with a prolyl residue; (ii) in cyclic tripeptides the internal angles viz., CαCN and CNCα are significantly larger thereby increasing the intra-annular space; (iii) the bond Cα-C is distinctly shorter when it occurs in cyclic dipeptides. The results lead to the conclusion that the cis peptide unit takes up a need-based flexibility in its dimension.

Cyclic peptides––Small and big and their conformational aspects.

Cyclic peptides form an interesting class of compounds for study by conformational analysis, by virtue of their unique conformational features and biological properties. The small cyclic peptides having 3–6 peptide units in their ring, show a variety of conformational characteristics such as occurrence of cis peptide units, flexibility of peptide dimension and variety in hydrogen bonding. The different possible conformations of cyclic triand hexa-peptides are given and certain specific conformational features are discussed for cyclic tetra and pentapeptides. For higher cyclic peptides, the hydrogen bonding requirement for stability of the backbone of the ring, is seen to be kept to a minimum. These various features and their significance are examined and discussed in the light of energy minimization studies and analysis of available experimental data.