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@article{pmid42757708,

title = {Strategy for modular assembly of tetravalent, multispecific antibodies},

author = {Evan Mallette and Levi L Blazer and Craig A Hokanson and Chao Chen and Julia Garcia Perez and Alevtina Pavlenco and Lynda Ploder and Alexander U Singer and Michael D L Suits and Sunil Bhakta and Jagath R Junutula and Jarrett J Adams and Sachdev S Sidhu},

doi = {10.1002/pro.70797},

issn = {1469-896X},

year  = {2026},

date = {2026-10-01},

urldate = {2026-10-01},

journal = {Protein Sci},

volume = {35},

number = {10},

pages = {e70797},

abstract = {Multispecific, multivalent antibodies (Abs) are a burgeoning class of drugs that dramatically expand the pharmacological repertoire beyond traditional therapeutic Abs. Here, we present a simple, modular approach to developing multispecific, multivalent Abs based on a Fab-phage library with a single light chain. Using this library, we created three Abs targeting unique sites on programmed death-ligand 1 (PD-L1) and another antibody targeting CD30. Biophysical and cellular characterization of these Abs demonstrated their functional equivalence to clinically relevant Abs targeting PD-L1 or CD30. We then combined these paratopes into a series of bispecific, tetravalent, triparatopic Abs that retained the functionality of the parental Abs. Structural analysis of each of the Abs in complex with their cognate antigens demonstrated the adaptability of the common light chain to form diverse paratopes with an array of distinct heavy chains.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid41807832,

title = {Structures of ALG3/9/12 reveal the assembly logic of the N-glycan oligomannose core},

author = {J Andrew N Alexander and Shu-Yu Chen and Somnath Mukherjee and Mario de Capitani and Rossitza N Irobalieva and Lorenzo Rossi and Parth Agrawal and Julia Kowal and Matheus A Meirelles and Markus Aebi and Jean-Louis Reymond and Anthony A Kossiakoff and Sereina Riniker and Kaspar P Locher},

doi = {10.1038/s41589-026-02164-7},

issn = {1552-4469},

year  = {2026},

date = {2026-09-01},

urldate = {2026-09-01},

journal = {Nat Chem Biol},

volume = {22},

number = {9},

pages = {1501--1513},

abstract = {Asparagine-linked glycans are essential for the maturation and function of most eukaryotic secretory proteins. The biosynthesis and transfer of dolichylpyrophosphate-anchored GlcNAcManGlc glycan is a highly conserved process occurring in the endoplasmic reticulum (ER) membrane and involving over a dozen membrane proteins whose dysfunction is linked to congenital disorders of glycosylation (CDGs). Three membrane-integral mannosyltransferases, ALG3, ALG9 and ALG12, mediate four consecutive mannosylation reactions that convert GlcNAcMan to GlcNAcMan. Here, using chemoenzymatically synthesized lipid-linked glycan donor and acceptor analogs, we recapitulated this biosynthetic pathway in vitro. High-resolution cryo-electron microscopy structures of pseudo-Michaelis complexes of each step revealed how the branched glycan is accurately synthesized and unwanted side products are averted. Molecular dynamics simulations and mutagenesis studies uncovered a subtle but precise mechanism selecting the dolichylphosphomannose donor substrate over dolichylphosphoglucose, which is also present in the ER membrane. Our results also provide mechanistic explanations for enzyme dysfunction in CDGs and offer opportunities for N-glycan engineering.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid42290195,

title = {Clarifying Frizzled 2 function in development through genetically validated mouse models},

author = {Megan N Michalski and Cassandra R Diegel and Zhendong A Zhong and Maddison E Marshall and Gabrielle E Foxa Wiartalla and Payton D Stevens and Kelly Suino-Powell and Levi L Blazer and Jarrett J Adams and Karsten Melcher and Sachdev S Sidhu and Stephane Angers and Bart O Williams},

doi = {10.1242/dmm.052410},

issn = {1754-8411},

year  = {2026},

date = {2026-07-01},

urldate = {2026-07-01},

journal = {Dis Model Mech},

volume = {19},

number = {7},

abstract = {Wnt receptors of the Frizzled (Fzd) family are widely considered to exhibit substantial functional redundancy, complicating efforts to therapeutically target individual receptors. Fzd2 was believed to be functionally redundant with Fzd1 and Fzd7, based on previously published global knockout mouse studies. By contrast, homozygosity for a Fzd2 global knockout mouse allele developed by the International Mouse Phenotype Consortium (IMPC) has been reported to cause embryonic lethality, suggesting that Fzd2 is critical for early embryonic development. If global deletion of Fzd2 leads to early lethality, conditional deletion models are necessary to identify tissue-specific phenotypes. We found that a previously published Fzd2 conditional deletion model does not eliminate Fzd2. We have generated a new conditional model to address the contradictory previous studies and allow tissue-specific studies of Fzd2. We successfully inserted two loxP sites around the Fzd2 gene and confirmed that subsequent Cre-mediated recombination creates a Fzd2 null allele. Global deletion of Fzd2 in this model does not cause embryonic lethality while limb-specific deletion causes limb shortening. This work supports the hypothesis that Fzd2 regulates limb development and emphasizes the importance of thoroughly validating newly generated mouse models.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}