14 research outputs found
The Lantern, 2014-2015
• The Retreat • Part of Eve\u27s Discussion • Buchanan • Hypotheticals • The Baby Hippo • Sertraline and Cheerios • Margins • Anatomy of Me • Orange • Ode to Mathematics • Garden Path • Periphery • 10n Power=Our Maybe Domains • Hillside • Baltimore//Analogues • Work is a Religion • At the Bridal Shower • November • Revisionist History • Cold Front • Lung (for D. Avitabile) • Tether • Hold Still • Reverb • An Almost English Major and His Daughter • Clocks • In the Kitchen on a Sunday Afternoon • Amy • Nine • Customary Thoughts • Showers • Te Encuentro • I Find You • Literary Analysis • The Diamond on My Face • Catherine • Hunsberger Woods, 11:42 on a School Night • Cabbage • After Class • For Chell • To Whom It May Concern • Contra • Shards • Smoke and Roses • Polaroid • Spring\u27s Debut • The Deadline • A Previous Life • Wet Canvas • Obsessions and Compulsions • For Xandra • The Seagulls of 17th Street • No Man\u27s Land • Summer Flowers • Float • Dana Reads • A Barcelona Moment • Business Meeting • Posted • Champagnehttps://digitalcommons.ursinus.edu/lantern/1181/thumbnail.jp
The Lantern, 2015-2016
• Ghosts • Going to China • 98% Guaranteed • Constellation/Boulevard • Prayer • The Little One • Burning • The Amber Macaroon • Becoming • Requiem • Construction Site • Thirteen Ways of Looking at a Dragon • Charlie • No Sleep • A Lesson in Physical Education • Statues • Who Can Love a Black Woman? • Apples • Fun Craft • The Door at Midnight • Eve as a Book in the Bible • Boys • Diamond Heart • To Apollo • Joanne and Her July Garden • Option A, 1936 • Young White Girls, Hollow Bodies, and Home • Mama\u27s Stance on Sugar • The Mariana Trench • Hurricane • Part of the Job • Avenue H Blues • Hour of Nones • Send Toilet Paper • Grave Robbing • Wild Turkey • The Creek • Let\u27s Go for a Walk • Deaconess • Border of Love • Your Father, Rumpelstiltskin • Purchasing Poplars • Red Tatters • Sunken • Whispers • Existence • God Took a Cigarette Break with Police Officers • Martian Standoff • In the Headlights • It\u27s a Subtle Thing • Dear Kent • Hanako-san • A Brief Interlude • On Fencing, Gummy Worms, and my Inescapable Fear of Living in the Moment • Stolen Soul • Block • Mortem Mei Fratris • Kalki • Lake Placid • Atom and Eve • The Baerie Queene • Gladston • Soldiers at Gettysburg • Pattern • Foliage • Mass Media • Arrow • Move Out • Wanderers • Riverside Gardenhttps://digitalcommons.ursinus.edu/lantern/1182/thumbnail.jp
Specificity, affinity and efficacy of iota-conotoxin RXIA, an agonist of voltage-gated sodium channels NaV1.2, 1.6 and 1.7
Discovery of Peptidomimetic Antibody–Drug Conjugate Linkers with Enhanced Protease Specificity
Antibody–drug
conjugates (ADCs) have become an important
therapeutic modality for oncology, with three approved by the FDA
and over 60 others in clinical trials. Despite the progress, improvements
in ADC therapeutic index are desired. Peptide-based ADC linkers that
are cleaved by lysosomal proteases have shown sufficient stability
in serum and effective payload-release in targeted cells. If the linker
can be preferentially hydrolyzed by tumor-specific proteases, safety
margin may improve. However, the use of peptide-based linkers limits
our ability to modulate protease specificity. Here we report the structure-guided
discovery of novel, nonpeptidic ADC linkers. We show that a cyclobutane-1,1-dicarboxamide-containing
linker is hydrolyzed predominantly by cathepsin B while the valine–citrulline
dipeptide linker is not. ADCs bearing the nonpeptidic linker are as
efficacious and stable in vivo as those with the dipeptide linker.
Our results strongly support the application of the peptidomimetic
linker and present new opportunities for improving the selectivity
of ADCs
Discovery of Peptidomimetic Antibody–Drug Conjugate Linkers with Enhanced Protease Specificity
Antibody–drug
conjugates (ADCs) have become an important
therapeutic modality for oncology, with three approved by the FDA
and over 60 others in clinical trials. Despite the progress, improvements
in ADC therapeutic index are desired. Peptide-based ADC linkers that
are cleaved by lysosomal proteases have shown sufficient stability
in serum and effective payload-release in targeted cells. If the linker
can be preferentially hydrolyzed by tumor-specific proteases, safety
margin may improve. However, the use of peptide-based linkers limits
our ability to modulate protease specificity. Here we report the structure-guided
discovery of novel, nonpeptidic ADC linkers. We show that a cyclobutane-1,1-dicarboxamide-containing
linker is hydrolyzed predominantly by cathepsin B while the valine–citrulline
dipeptide linker is not. ADCs bearing the nonpeptidic linker are as
efficacious and stable in vivo as those with the dipeptide linker.
Our results strongly support the application of the peptidomimetic
linker and present new opportunities for improving the selectivity
of ADCs
Discovery of Peptidomimetic Antibody–Drug Conjugate Linkers with Enhanced Protease Specificity
Antibody–drug
conjugates (ADCs) have become an important
therapeutic modality for oncology, with three approved by the FDA
and over 60 others in clinical trials. Despite the progress, improvements
in ADC therapeutic index are desired. Peptide-based ADC linkers that
are cleaved by lysosomal proteases have shown sufficient stability
in serum and effective payload-release in targeted cells. If the linker
can be preferentially hydrolyzed by tumor-specific proteases, safety
margin may improve. However, the use of peptide-based linkers limits
our ability to modulate protease specificity. Here we report the structure-guided
discovery of novel, nonpeptidic ADC linkers. We show that a cyclobutane-1,1-dicarboxamide-containing
linker is hydrolyzed predominantly by cathepsin B while the valine–citrulline
dipeptide linker is not. ADCs bearing the nonpeptidic linker are as
efficacious and stable in vivo as those with the dipeptide linker.
Our results strongly support the application of the peptidomimetic
linker and present new opportunities for improving the selectivity
of ADCs