Oligopeptides with Equal Amounts of l- and d‑Amino Acids May Prefer a Helix Screw Sense

We investigated the preferred conformations of two nonapeptides, Boc-(l-Leu-d-Leu-Aib)₃-OMe (<b>2</b>) and its enantiomer Boc-(d-Leu-l-Leu-Aib)₃-OMe (<i>ent</i>-<b>2</b>), four dodecapeptides, Boc-(l-Leu-d-Leu-Aib)₄-OMe (<b>3</b>), Boc-(l-Leu-Aib-d-Leu)₄-OMe (<b>4</b>), Boc-(Aib-l-Leu-d-Leu)₄-OMe (<b>5</b>), and Boc-(l-Leu-Aib-d-Leu-Aib)₃-OMe (<b>6</b>), and a decapeptide, Boc-l-Leu-(d-Leu-l-Leu-Aib)₃-OMe (<b>7</b>), in solution and in the crystalline state. The nonapeptide <b>2</b> formed a right-handed (<i>P</i>) α-helix, and its enantiomer <i>ent</i>-<b>2</b> formed a left-handed (<i>M</i>) α-helix. The dodecapeptides <b>3</b> and <b>5</b> were folded into (<i>P</i>) helices, and <b>4</b> formed an (<i>M</i>) helical structure. As for <b>6</b>, roughly equivalent amounts of (<i>P</i>) and (<i>M</i>) helices were observed in solution, and two (<i>M</i>) α-helices were detected in the crystalline state. Furthermore, the decapeptide <b>7</b>, which possesses four l-Leu residues and three d-Leu residues, was folded into an (<i>M</i>) α-helix

Oligopeptides with Equal Amounts of l- and d‑Amino Acids May Prefer a Helix Screw Sense

We investigated the preferred conformations of two nonapeptides, Boc-(l-Leu-d-Leu-Aib)₃-OMe (<b>2</b>) and its enantiomer Boc-(d-Leu-l-Leu-Aib)₃-OMe (<i>ent</i>-<b>2</b>), four dodecapeptides, Boc-(l-Leu-d-Leu-Aib)₄-OMe (<b>3</b>), Boc-(l-Leu-Aib-d-Leu)₄-OMe (<b>4</b>), Boc-(Aib-l-Leu-d-Leu)₄-OMe (<b>5</b>), and Boc-(l-Leu-Aib-d-Leu-Aib)₃-OMe (<b>6</b>), and a decapeptide, Boc-l-Leu-(d-Leu-l-Leu-Aib)₃-OMe (<b>7</b>), in solution and in the crystalline state. The nonapeptide <b>2</b> formed a right-handed (<i>P</i>) α-helix, and its enantiomer <i>ent</i>-<b>2</b> formed a left-handed (<i>M</i>) α-helix. The dodecapeptides <b>3</b> and <b>5</b> were folded into (<i>P</i>) helices, and <b>4</b> formed an (<i>M</i>) helical structure. As for <b>6</b>, roughly equivalent amounts of (<i>P</i>) and (<i>M</i>) helices were observed in solution, and two (<i>M</i>) α-helices were detected in the crystalline state. Furthermore, the decapeptide <b>7</b>, which possesses four l-Leu residues and three d-Leu residues, was folded into an (<i>M</i>) α-helix

Topological Study of the Structures of Heterochiral Peptides Containing Equal Amounts of l‑Leu and d‑Leu

We designed and synthesized two dodecapeptides, Boc-(l-Leu-l-Leu-Aib-d-Leu-d-Leu-Aib)₂-OMe (<b>5</b>) and Boc-l-Leu-l-Leu-Aib-(d-Leu-d-Leu-Aib)₂-l-Leu-l-Leu-Aib-OMe (<b>6</b>), that contain equal amounts of l-Leu, d-Leu, and achiral Aib residues. The conformations of peptides <b>5</b> and <b>6</b> in the crystalline state were studied using X-ray crystallographic analysis. Peptide <b>5</b> formed a left-handed (<i>M</i>) α-helical structure, whereas peptide <b>6</b> was composed of a combination of fused (<i>M</i>) α-helical and right-handed (<i>P</i>) 3₁₀-helical structures. In solution, roughly equivalent amounts of (<i>P</i>) and (<i>M</i>) helices were present in <b>5</b>, whereas the (<i>M</i>) α-helix was present in <b>6</b> as its dominant conformation

Oligopeptides with Equal Amounts of l- and d‑Amino Acids May Prefer a Helix Screw Sense

We investigated the preferred conformations of two nonapeptides, Boc-(l-Leu-d-Leu-Aib)₃-OMe (<b>2</b>) and its enantiomer Boc-(d-Leu-l-Leu-Aib)₃-OMe (<i>ent</i>-<b>2</b>), four dodecapeptides, Boc-(l-Leu-d-Leu-Aib)₄-OMe (<b>3</b>), Boc-(l-Leu-Aib-d-Leu)₄-OMe (<b>4</b>), Boc-(Aib-l-Leu-d-Leu)₄-OMe (<b>5</b>), and Boc-(l-Leu-Aib-d-Leu-Aib)₃-OMe (<b>6</b>), and a decapeptide, Boc-l-Leu-(d-Leu-l-Leu-Aib)₃-OMe (<b>7</b>), in solution and in the crystalline state. The nonapeptide <b>2</b> formed a right-handed (<i>P</i>) α-helix, and its enantiomer <i>ent</i>-<b>2</b> formed a left-handed (<i>M</i>) α-helix. The dodecapeptides <b>3</b> and <b>5</b> were folded into (<i>P</i>) helices, and <b>4</b> formed an (<i>M</i>) helical structure. As for <b>6</b>, roughly equivalent amounts of (<i>P</i>) and (<i>M</i>) helices were observed in solution, and two (<i>M</i>) α-helices were detected in the crystalline state. Furthermore, the decapeptide <b>7</b>, which possesses four l-Leu residues and three d-Leu residues, was folded into an (<i>M</i>) α-helix

Examples of ‘parenchyma rate in’ parameter (also Fig 3B) maps from a non-triple-negative (TN) patient (left) and a TN patient (right) illustrating the difference of a statistical texture feature between members of the two groups in image form.

<p>Slices of the ‘parenchyma rate in’ parameter map void of tumor tissue are presented in the sagittal plane. It is evident the variation of this background parenchymal enhancement texture feature’s value is greater in TN cancers, where standard deviation is markedly higher at 352.9 as opposed to 133.8 in the non-TN patient.</p

Example of tissue segmentation performed of all cancer patients’ affected breast images.

<p>At top left (a), a dynamic contrast-enhanced MRI exam at t3 is seen in the axial plane, illustrating one slice of the view used for contouring the breast and tumor. At top right (b), the result of breast segmentation is shown. At bottom left (c), the segmented tumor is highlighted in blue. Finally at bottom right (d), the parenchyma segmented at t1 is highlighted in pink. Breast subcompartment segmentation was performed in 3-dimensions.</p

Unsupervised <i>k</i>-means clustering of breast cancer patients (n = 88) on the x-axis and quantitative background parenchymal enhancement (BPE) feature expression (n = 39) on y-axis (as z-scores, with scale at bottom left. std = standard deviation).

<p>Correspondence of patient groups with similar radiomic expression patterns can be seen where the majority of triple-negative (TN) breast cancers have grouped together in the left cluster (9 of 11 TN in partition highlighted orange at top left) due to association of the BPE heterogeneity feature signatures. 1^st order statistical texture features are highlighted as purple and similarly 2^nd order statistical texture features are green at right indicating correspondence of feature groups with clustered expression patterns.</p

The effect of adjuvant systemic therapy on prognostic impact of polymorphisms

<p><b>Copyright information:</b></p><p>Taken from "Association of codon 72 polymorphism and the outcome of adjuvant therapy in breast cancer patients"</p><p>http://breast-cancer-research.com/content/9/3/R34</p><p>Breast Cancer Research 2007;9(3):R34-R34.</p><p>Published online 30 May 2007</p><p>PMCID:PMC1929098.</p><p></p> codon 72 and adjuvant chemotherapy alone (= 137); codon 72 and adjuvant chemotherapy with or without hormonal therapy (= 281); codon 72 and adjuvant hormonal therapy alone (= 195); codon 72 and no adjuvant systemic therapy (= 77); SNP309 and adjuvant tamoxifen with or without luteinizing hormone-releasing hormone analog (= 185). DFS, disease-free survival

Summary of radiomic analysis performed in this study.

<p>Clinical features were evaluated by a radiologist according to Breast Imaging Reporting and Data System directly from dynamic contrast-enhanced MRI (a). 3-Dimensional tumor (red) and parenchyma (light blue) compartments were segmented (b), from which volumetric breast density was immediately estimated (c). Enhancement maps were then generated (d), from which textural features of tissue compartments were extracted and defined as enhancement heterogeneity (e). Subsequently, two analyses were conducted using extracted features: supervised learning of breast cancer subtype was performed with a support vector machine classifier (f) and unsupervised learning of background parenchymal enhancement feature expression pattern was performed with <i>k</i>-means clustering (g).</p

Box plots illustrating differences in distributions (quartiles as red boxes, grand mean indicated as spanning line) of the three most predictive quantitative features found in differentiation tasks: the lesion’s ‘mass size’ feature (a), parenchyma’s ‘skewness of Signal Enhancement Ratio’ feature (b), and parenchyma’s ‘standard deviation of rate in’ feature (c) compared between the triple-negative (TN) and non-TN groups.

<p>p-values were calculated by Wilcoxon Mann-Whitney tests.</p