Full Text Journal Articles by
Author Juan R Del Valle

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STING regulates BCR signaling in normal and malignant B cells.

Chih-Hang Anthony Tang, Avery C Lee, Shiun Chang, Qin Xu, Andong Shao, Yun Lo, Walker T Spalek, Javier A Pinilla-Ibarz, Juan R Del Valle, Chih-Chi Andrew Hu,

STING is an endoplasmic reticulum (ER)-resident protein critical for sensing cytoplasmic DNA and promoting the production of type I interferons; however, the role of STING in B cell receptor (BCR) signaling remains unclear. We generated STING V154M knock-in mice and showed that B cells carrying constitutively activated STING specifically degraded ... Read more >>

Cell Mol Immunol (Cellular & molecular immunology)
[2020, :]

Cited: 0 times

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Development of tumor-targeting IRE-1 inhibitors for B cell cancer therapy.

Andong Shao, Qin Xu, Walker T Spalek, Christopher F Cain, Chang Won Kang, Chih-Hang Anthony Tang, Juan R Del Valle, Chih-Chi Andrew Hu,

The IRE-1 kinase/RNase splices the mRNA of the XBP-1 gene, resulting in the spliced XBP-1 (XBP-1s) mRNA that encodes the functional XBP-1s transcription factor that is critically important for the growth and survival of B-cell leukemia, lymphoma and multiple myeloma (MM). Several inhibitors targeting the expression of XBP-1s have been ... Read more >>

Mol Cancer Ther (Molecular cancer therapeutics)
[2020, :]

Cited: 0 times

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Clarifying the translational potential of B-I09.

Juan R Del Valle, Brian C Betts, Xue-Zhong Yu, Sophie Janssens, Bart N Lambrecht, M Celeste Simon, Chih-Chi Andrew Hu,

Nat Chem Biol (Nature chemical biology)
[2020, 16(11):1152]

Cited: 0 times

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Synthesis and biological evaluation of backbone-aminated analogues of gramicidin S.

Benjamin M Rathman, Jessie L Allen, Lindsey N Shaw, Juan R Del Valle,

We report the parallel synthesis of gramicidin S derivatives featuring backbone N-amino substituents. Analogues were prepared by incorporation of N-amino dipeptide subunits on solid support. Nine backbone-aminated macrocycles were evaluated for growth inhibitory activity against ESKAPE pathogens and hemolytic activity against human red blood cells. Diamination of the Orn residues ... Read more >>

Bioorg. Med. Chem. Lett. (Bioorganic & medicinal chemistry letters)
[2020, 30(15):127283]

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δ-Azaproline and Its Oxidized Variants.

Yassin M Elbatrawi, Kyle P Pedretty, Nicole Giddings, H Lee Woodcock, Juan R Del Valle,

Peptides featuring backbone N-amino substituents exhibit unique conformational properties owing to additional electrostatic, hydrogen-bonding, and steric interactions. Here, we describe the synthesis and conformational analysis of three δ-azaproline derivatives as potential proline surrogates. Our studies demonstrate stereoelectronic tuning of heterocyclic ring pucker, cis/trans amide propensity, and amide isomerization barriers within ... Read more >>

J. Org. Chem. (The Journal of organic chemistry)
[2020, 85(6):4207-4219]

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N-Hydroxy peptides: solid-phase synthesis and β-sheet propensity.

Matthew P Sarnowski, Juan R Del Valle,

Peptide backbone amide substitution can dramatically alter the conformational and physiochemical properties of native sequences. Although uncommon relative to N-alkyl substituents, peptides harboring main-chain N-hydroxy groups exhibit unique conformational preferences and biological activities. Here, we describe a versatile method to prepare N-hydroxy peptide on solid support and evaluate the impact ... Read more >>

Org Biomol Chem (Organic & biomolecular chemistry)
[2020, 18(19):3690-3696]

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Synthesis of Enantiopure ε-Oxapipecolic Acid.

Evan H Howard, Christopher F Cain, Changwon Kang, Juan R Del Valle,

A six-step synthesis of orthogonally protected (S)-ε-oxapipecolic acid is described, starting from a commercially available glutamate diester. The approach features mCPBA-mediated amine oxidation and an intramolecular Mitsunobu reaction to form the tetrahydrooxazine ring. The enantiopure building block was employed in the synthesis of a short model peptide to determine the ... Read more >>

J. Org. Chem. (The Journal of organic chemistry)
[2020, 85(3):1680-1686]

Cited: 0 times

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Inhibition of Human Dendritic Cell ER Stress Response Reduces T Cell Alloreactivity Yet Spares Donor Anti-tumor Immunity.

Brian C Betts, Frederick L Locke, Elizabeth M Sagatys, Joseph Pidala, Kelly Walton, Meghan Menges, Jordan Reff, Asim Saha, Julie Y Djeu, John V Kiluk, Marie C Lee, Jongphil Kim, Chang Won Kang, Chih-Hang Tang, Jeremy Frieling, Conor C Lynch, Alan List, Paulo C Rodriguez, Bruce R Blazar, Jose R Conejo-Garcia, Juan R Del Valle, Chih-Chi Hu, Claudio Anasetti,

Acute graft- vs. -host disease (GVHD) is an important cause of morbidity and death after allogeneic hematopoietic cell transplantation (HCT). We identify a new approach to prevent GVHD that impairs monocyte-derived dendritic cell (moDC) alloactivation of T cells, yet preserves graft- vs.-leukemia (GVL). Exceeding endoplasmic reticulum (ER) capacity results in ... Read more >>

Front Immunol (Frontiers in immunology)
[2018, 9:2887]

Cited: 6 times

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Phosphorylation of IRE1 at S729 regulates RIDD in B cells and antibody production after immunization.

Chih-Hang Anthony Tang, Shiun Chang, Adrienne W Paton, James C Paton, Dmitry I Gabrilovich, Hidde L Ploegh, Juan R Del Valle, Chih-Chi Andrew Hu,

To relieve endoplasmic reticulum (ER) stress, IRE1 splices XBP1 messenger RNA (mRNA) or engages regulated IRE1-dependent decay (RIDD) of other mRNAs. Upon XBP1 deficiency, IRE1 switches to perform RIDD. We examined IRE1 in XBP1-deficient B cells and discovered that IRE1 undergoes phosphorylation at S729. We generated an anti-phospho-S729 antibody to ... Read more >>

J. Cell Biol. (The Journal of cell biology)
[2018, 217(5):1739-1755]

Cited: 8 times

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Secretory IgM Exacerbates Tumor Progression by Inducing Accumulations of MDSCs in Mice.

Chih-Hang Tang, Shiun Chang, Ayumi Hashimoto, Yi-Ju Chen, Chang Won Kang, Anthony R Mato, Juan R Del Valle, Dmitry I Gabrilovich, Chih-Chi Hu,

Chronic lymphocytic leukemia (CLL) cells can secrete immunoglobulin M. However, it is not clear whether secretory IgM (sIgM) plays a role in disease progression. We crossed the Eμ-TCL1 mouse model of CLL, in which the expression of human TCL1 oncogene was driven by the V(H) promoter-Ig(H)-Eμ enhancer, with MD4 mice ... Read more >>

Cancer Immunol Res (Cancer immunology research)
[2018, 6(6):696-710]

Cited: 4 times

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IRE1α RNase-dependent lipid homeostasis promotes survival in Myc-transformed cancers.

Hong Xie, Chih-Hang Anthony Tang, Jun H Song, Anthony Mancuso, Juan R Del Valle, Jin Cao, Yan Xiang, Chi V Dang, Roy Lan, Danielle J Sanchez, Brian Keith, Chih-Chi Andrew Hu, M Celeste Simon,

Myc activation is a primary oncogenic event in many human cancers; however, these transcription factors are difficult to inhibit pharmacologically, suggesting that Myc-dependent downstream effectors may be more tractable therapeutic targets. Here, we show that Myc overexpression induces endoplasmic reticulum (ER) stress and engages the inositol-requiring enzyme 1α (IRE1α)/X-box binding ... Read more >>

J Clin Invest (The Journal of clinical investigation)
[2018, 128(4):1300-1316]

Cited: 7 times

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Total Synthesis of L-156,373 and an oxoPiz Analogue via a Submonomer Approach.

Yassin M Elbatrawi, Chang Won Kang, Juan R Del Valle,

The first chemical synthesis of L-156,373 (1), a potent oxytocin receptor antagonist isolated from Streptomyces silvensis, is reported. Assembly of the unusual d-Piz-l-Piz dipeptide subunit was achieved through a sequential electrophilic amination-acylation-deprotection strategy followed by late-stage Piz ring formation. Synthesis and incorporation of a novel N-hydroxy-l-isoleucine building block is also ... Read more >>

Org Lett (Organic letters)
[2018, 20(9):2707-2710]

Cited: 1 time

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Inhibition of the IRE-1α/XBP-1 pathway prevents chronic GVHD and preserves the GVL effect in mice.

Steven D Schutt, Yongxia Wu, Chih-Hang Anthony Tang, David Bastian, Hung Nguyen, M Hanief Sofi, MengMeng Zhang, Chen Liu, Kris Helke, Carole Wilson, Lynn M Schnapp, Juan R Del Valle, Chih-Chi Andrew Hu, Xue-Zhong Yu,

Hematopoietic stem cell transplantation (HCT) is a curative procedure for hematological malignancies, but chronic graft-versus-host disease (cGVHD) remains a major complication after allogeneic HCT. Because donor B cells are essential for cGVHD development and B cells are sensitive to endoplasmic reticulum (ER) stress, we hypothesized that the IRE-1α/XBP-1 pathway is ... Read more >>

Blood Adv (Blood advances)
[2018, 2(4):414-427]

Cited: 8 times

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Synthesis and β-sheet propensity of constrained N-amino peptides.

Matthew P Sarnowski, Kyle P Pedretty, Nicole Giddings, H Lee Woodcock, Juan R Del Valle,

The stabilization of β-sheet secondary structure through peptide backbone modification represents an attractive approach to protein mimicry. Here, we present strategies toward stable β-hairpin folds based on peptide strand N-amination. Novel pyrazolidinone and tetrahydropyridazinone dipeptide constraints were introduced via on-resin Mitsunobu cyclization between α-hydrazino acid residues and a serine or ... Read more >>

Bioorg. Med. Chem. (Bioorganic & medicinal chemistry)
[2018, 26(6):1162-1166]

Cited: 0 times

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Access to Enantiopure α-Hydrazino Acids for N-Amino Peptide Synthesis.

Chang Won Kang, Matthew P Sarnowski, Yassin M Elbatrawi, Juan R Del Valle,

Backbone N-methylation of α-peptides has been widely employed to enhance the bioavailability and bioactivity of parent sequences. Heteroatomic peptide amide substituents have received less attention due, in part, to the lack of practical synthetic strategies. Here, we report the synthesis of α-hydrazino acids derived from 19 out of the 20 ... Read more >>

J. Org. Chem. (The Journal of organic chemistry)
[2017, 82(3):1833-1841]

Cited: 2 times

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Peptide N-Amination Supports β-Sheet Conformations.

Matthew P Sarnowski, Chang Won Kang, Yassin M Elbatrawi, Lukasz Wojtas, Juan R Del Valle,

The conformational heterogeneity of backbone N-substituted peptides limits their ability to adopt stable secondary structures. Herein, we describe a practical synthesis of backbone aminated peptides that readily adopt β-sheet folds. Data derived from model N-amino peptides suggest that extended conformations are stabilized through cooperative steric, electrostatic, and hydrogen-bonding interactions. ... Read more >>

Angew. Chem. Int. Ed. Engl. (Angewandte Chemie (International ed. in English))
[2017, 56(8):2083-2086]

Cited: 5 times

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Regulated IRE1-dependent mRNA decay sets the threshold for dendritic cell survival.

Simon J Tavernier, Fabiola Osorio, Lana Vandersarren, Jessica Vetters, Nele Vanlangenakker, Gert Van Isterdael, Karl Vergote, Riet De Rycke, Eef Parthoens, Lianne van de Laar, Takao Iwawaki, Juan R Del Valle, Chih-Chi Andrew Hu, Bart N Lambrecht, Sophie Janssens,

The IRE1-XBP1 signalling pathway is part of a cellular programme that protects against endoplasmic reticulum (ER) stress, but also controls development and survival of immune cells. Loss of XBP1 in splenic type 1 conventional dendritic cells (cDC1s) results in functional alterations without affecting cell survival. However, in mucosal cDC1s, loss ... Read more >>

Nat Cell Biol (Nature cell biology)
[2017, 19(6):698-710]

Cited: 26 times

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Agonist-Mediated Activation of STING Induces Apoptosis in Malignant B Cells.

Chih-Hang Anthony Tang, Joseph A Zundell, Sujeewa Ranatunga, Cindy Lin, Yulia Nefedova, Juan R Del Valle, Chih-Chi Andrew Hu,

Endoplasmic reticulum (ER) stress responses through the IRE-1/XBP-1 pathway are required for the function of STING (TMEM173), an ER-resident transmembrane protein critical for cytoplasmic DNA sensing, IFN production, and cancer control. Here we show that the IRE-1/XBP-1 pathway functions downstream of STING and that STING agonists selectively trigger mitochondria-mediated apoptosis ... Read more >>

Cancer Res (Cancer research)
[2016, 76(8):2137-2152]

Cited: 53 times

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β-Strand mimics based on tetrahydropyridazinedione (tpd) peptide stitching.

Chang Won Kang, Matthew P Sarnowski, Sujeewa Ranatunga, Lukasz Wojtas, Rainer S Metcalf, Wayne C Guida, Juan R Del Valle,

Short peptides featuring a tetrahydropyridazinedione (tpd) backbone tether exhibit reduced conformational flexibility external to the heterocyclic constraint. Analysis by NMR, molecular modeling and X-ray crystallography suggests both covalent and non-covalent stabilization of extended peptide conformations. An efficient solid-phase protocol was developed for the synthesis of a new class of β-strand ... Read more >>

Chem Commun (Camb) (Chemical communications (Cambridge, England))
[2015, 51(90):16259-16262]

Cited: 3 times

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Solid-phase synthesis of tetrahydropyridazinedione-constrained peptides.

Chang Won Kang, Sujeewa Ranatunga, Matthew P Sarnowski, Juan R Del Valle,

The design and solid-phase synthesis of tetrahydropyridazine-3,6-dione (Tpd) peptidomimetics derived from backbone-aminated peptides is reported. The described protocol features the synthesis of chiral α-hydrazino acids suitable for chemoselective incorporation into growing peptide chains. Acid-catalyzed cyclization to form the Tpd ring during cleavage affords the target peptidomimetics in good yield and ... Read more >>

Org. Lett. (Organic letters)
[2014, 16(20):5434-5437]

Cited: 3 times

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Inhibition of ER stress-associated IRE-1/XBP-1 pathway reduces leukemic cell survival.

Chih-Hang Anthony Tang, Sujeewa Ranatunga, Crystina L Kriss, Christopher L Cubitt, Jianguo Tao, Javier A Pinilla-Ibarz, Juan R Del Valle, Chih-Chi Andrew Hu,

Activation of the ER stress response is associated with malignant progression of B cell chronic lymphocytic leukemia (CLL). We developed a murine CLL model that lacks the ER stress-associated transcription factor XBP-1 in B cells and found that XBP-1 deficiency decelerates malignant progression of CLL-associated disease. XBP-1 deficiency resulted in ... Read more >>

J. Clin. Invest. (The Journal of clinical investigation)
[2014, 124(6):2585-2598]

Cited: 75 times

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Imidazo[1,2-a]pyridine-based peptidomimetics as inhibitors of Akt.

Young B Kim, Chang Won Kang, Sujeewa Ranatunga, Hua Yang, Said M Sebti, Juan R Del Valle,

We report the design, synthesis, and biological evaluation of imidazopyridine-based peptidomimetics based on the substrate consensus sequence of Akt, an AGC family serine/threonine kinase hyperactivated in over 50% of human tumors. Our ligand-based approach led to the identification of novel substrate mimetic inhibitors of Akt1 featuring an unnatural extended dipeptide ... Read more >>

Bioorg Med Chem Lett (Bioorganic & medicinal chemistry letters)
[2014, 24(19):4650-4653]

Cited: 3 times

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Structure assignment of lucentamycin E and revision of the olefin geometries of the marine-derived lucentamycins.

Jin Wook Cha, Jin-Soo Park, Taebo Sim, Sang-Jip Nam, Hak Cheol Kwon, Juan R Del Valle, William Fenical,

A new lucentamycin analogue, lucentamycin E (5), was isolated from the culture broth of the marine-derived actinomycete Nocardiopsis lucentensis, strain CNR-712. The absolute stereostructure of 5 was assigned by comprehensive analyses of NMR data and by application of the advanced Marfey's method. The planar structure of 5 was analogous to ... Read more >>

J Nat Prod (Journal of natural products)
[2012, 75(9):1648-1651]

Cited: 4 times

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Substituted imidazo[1,2-a]pyridines as β-strand peptidomimetics.

Chang Won Kang, Yongmao Sun, Juan R Del Valle,

New conformationally extended dipeptide surrogates based on an imidazo[1,2-a]pyridine scaffold are described. Efficient synthesis and incorporation into host peptides affords structures with native side-chain functionality and hydrogen bonding elements on one face of the backbone. Structural analysis by NMR suggests that model peptidomimetics adopt a β-strand-like conformation in solution. ... Read more >>

Org Lett (Organic letters)
[2012, 14(24):6162-6165]

Cited: 5 times

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Synthesis and evaluation of substituted hexahydronaphthalenes as novel inhibitors of the Mcl-1/BimBH3 interaction.

Young B Kim, Maria E Balasis, Kenichiro Doi, Norbert Berndt, Courtney DuBoulay, Chih-Chi Andrew Hu, Wayne Guida, Hong-Gang Wang, Saïd M Sebti, Juan R Del Valle,

Mcl-1, an anti-apoptotic member of the Bcl-2 protein family, is overexpressed in a broad range of human cancers and plays a critical role in conferring resistance to chemotherapy. In the course of screening a natural product-like library of sesquiterpenoid analogs, we identified substituted hexahydronaphthalenes that showed activity against the Mcl-1/BimBH3 ... Read more >>

Bioorg Med Chem Lett (Bioorganic & medicinal chemistry letters)
[2012, 22(18):5961-5965]

Cited: 3 times

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