The RIGHT pro­tein and the case for cryo-EM with Pro­teros

The RIGHT pro­tein and the case for cryo-EM with Pro­teros

In the fast-evolv­ing land­scape of drug dis­cov­ery, struc­ture-based drug de­sign (SB­DD) stands as a cor­ner­stone. Specif­i­cal­ly, cryo-elec­tron mi­croscopy (cryo-EM) has show­cased tremen­dous util­i­ty with­in SB­DD. Cryo-EM SB­DD has en­abled ra­tio­nal drug de­sign for tar­gets that were pre­vi­ous­ly con­sid­ered in­tractable. How­ev­er, the de­vel­op­ment and main­te­nance of an in-house cryo-EM plat­form are be­yond the reach of most biotech firms, mak­ing the se­lec­tion of the ide­al Con­tract Re­search Or­ga­ni­za­tion (CRO) a piv­otal de­ci­sion. Pro­teros, based in Mu­nich, Ger­many, stands out in this are­na, aim­ing to el­e­vate struc­ture through­put, en­hance res­o­lu­tion, ex­pe­dite time­lines, and op­ti­mize cost-per-struc­ture, there­by tru­ly de­moc­ra­tiz­ing struc­ture-based drug de­sign for all tar­get-based drug dis­cov­ery en­deav­ors. High­light­ed ahead are the dis­tinc­tive strengths and unique at­trib­ut­es that ce­ment Pro­teros’ po­si­tion at the fore­front of the in­dus­try, set­ting us apart as a pi­o­neer­ing force in SB­DD.

The pri­ma­cy of pro­tein in cryo-EM

Just as ‘lo­ca­tion, lo­ca­tion, lo­ca­tion’ is the mantra in re­al es­tate, in the realm of cryo-EM it’s all about ‘pro­tein, pro­tein, pro­tein’. The chal­lenge is mag­ni­fied by the na­ture of pro­teins typ­i­cal­ly tar­get­ed by cryo-EM, many of which are no­to­ri­ous­ly dif­fi­cult to pro­duce. This is where our strength at Pro­teros shines. At Pro­teros, we spe­cial­ize in tack­ling the ‘high hang­ing fruit’ pro­teins that pose the great­est chal­lenges in the in­dus­try. With a for­mi­da­ble team of over 100 PhD-trained pro­tein sci­en­tists and ex­pe­ri­ence span­ning tens of thou­sands of pro­tein con­structs, we’re equipped to han­dle these in­tri­cate pro­teins. Our ded­i­ca­tion to ac­cel­er­at­ing drug dis­cov­ery is ev­i­dent in our com­mit­ment to es­tab­lish Gallery Struc­tures, an ini­tia­tive de­signed to cut down on time­lines and costs. The Gallery Struc­tures for cryo-EM at Pro­teros ex­pe­dite the process due to our ex­ten­sive ex­pe­ri­ence with these sys­tems, cou­pled with es­tab­lished method­olo­gies, pro­to­cols, and SOPs. This foun­da­tion en­ables the rapid de­ter­mi­na­tion of high-res­o­lu­tion re­peat struc­tures with cus­tomer-spe­cif­ic lig­ands, typ­i­cal­ly achieved with­in a few weeks and at com­pet­i­tive rates. The re­cent es­tab­lish­ment of GLP1R as a Gallery Struc­ture serves as a tes­ta­ment to this ef­fort. With our deep ex­per­tise, Pro­teros is poised to be the go-to so­lu­tion for in­tri­cate struc­tures, be it mem­brane pro­teins (such as GPCRs, ion chan­nels, solute car­ri­ers), small tar­gets, or large mul­ti-sub­unit com­plex­es.

Of­fer­ing an in­dus­tri­al­ized cryo-EM ser­vice from one hand

Hav­ing made sig­nif­i­cant strides in the in­dus­tri­al­iza­tion of pro­tein crys­tal­log­ra­phy, we’re now chan­nel­ing our ef­forts to shape the fu­ture of cryo-EM. At the heart of our ap­proach is the as­pi­ra­tion to un­rav­el even the most in­tri­cate of struc­tures. This re­quires not on­ly se­lect­ing the apt pro­tein but al­so lever­ag­ing state-of-the-art cryo-EM tech­nol­o­gy and our deep-root­ed ex­per­tise. Our cryo-EM team, with its di­verse skill set, spe­cial­izes in project eval­u­a­tion and cus­tomiza­tion in line with spe­cif­ic client re­quire­ments. They work dili­gent­ly to meet set goals in a time­ly man­ner. A key ad­van­tage is that Pro­teros’ in-house pro­tein and cryo-EM plat­forms can op­er­ate in tan­dem, pro­vid­ing dy­nam­ic in­sights that in­form and dri­ve sam­ple op­ti­miza­tion. This in­te­grat­ed ap­proach en­cap­su­lates our com­mit­ment to de­liv­er­ing an end-to-end, stream­lined cryo-EM ex­pe­ri­ence. Fur­ther­more, Pro­teros ac­knowl­edges the syn­er­gis­tic po­ten­tial of in­te­grat­ing both cryo-EM and crys­tal­log­ra­phy. Specif­i­cal­ly, while cryo-EM can guide con­struct de­sign for crys­tal­log­ra­phy, it al­so com­ple­ments the process by pro­vid­ing in­sights in­to pro­tein dy­nam­ics and re­veal­ing tran­sient states that may be elu­sive in crys­tal­lo­graph­ic sys­tems.

Eu­rope of­fers low costs and po­lit­i­cal sta­bil­i­ty

As a lead­ing struc­ture-based drug dis­cov­ery CRO, we pride our­selves on of­fer­ing a stream­lined ex­pe­ri­ence for our glob­al clien­tele. When clients pro­vide a pro­tein name, we take care of the rest, right up to de­liv­er­ing the atom­ic co­or­di­nates. Op­er­at­ing from Eu­rope po­si­tions us ad­van­ta­geous­ly, al­low­ing us to present so­lu­tions that are both cost-ef­fec­tive, align­ing well with the typ­i­cal­ly con­strained bud­gets of struc­tur­al bi­ol­o­gy, and sta­ble. In a world grap­pling with po­lit­i­cal flux, the con­sis­tent sta­bil­i­ty of Eu­rope of­fers the as­sur­ance that drug dis­cov­ery pro­grams and biotech in­vestors val­ue deeply.

Ac­cel­er­ate your dis­cov­ery with our holis­tic ap­proach

In con­clu­sion, Pro­teros is poised to el­e­vate the hori­zons of what can be achieved with cryo-EM in drug dis­cov­ery. Our ca­pa­bil­i­ties span a broad spec­trum of struc­tures and modal­i­ties, en­sur­ing that whether it’s mem­brane pro­teins, small tar­gets, mul­ti-sub­unit com­plex­es, tar­get­ed pro­tein degra­da­tion, gene ther­a­py, an­ti­body dis­cov­ery, or small mol­e­cule dis­cov­ery, we’ve got it cov­ered. And Pro­teros not on­ly ex­cels in cryo-EM ser­vices but al­so pro­vides a holis­tic ap­proach to drug dis­cov­ery through its Dis­cov­ery So­lu­tions. By in­te­grat­ing every es­sen­tial com­po­nent of the dis­cov­ery process, from the RIGHT pro­tein se­lec­tion, ad­vanced struc­tur­al bi­ol­o­gy, and cus­tomized as­say de­vel­op­ment to a di­verse range of screen­ing li­brary op­tions and com­pre­hen­sive bio­phys­i­cal mode-of-ac­tion method­olo­gies, Pro­teros en­sures that no stone is left un­turned in the pur­suit of po­ten­tial hit com­pounds.

To learn more about Pro­teros and how we can ac­cel­er­ate your drug dis­cov­ery ini­tia­tives, reach out to us. Our team of ex­perts is ea­ger to col­lab­o­rate and dri­ve your projects to fruition.


Mazdak Radjainia

Managing Director at cryoDuck and consultant for Proteros