Syrian peace talks, the Islamic State and Iran are expected to be high on the agenda in a pair of meetings Saturday that will see US Vice President Joe Biden in talks with Turkey's top leaders while US Secretary of State John Kerry heads to Saudi Arabia.
Both US officials leaders were coming from Switzerland. They are keen to press Ankara and Riyadh about which opposition groups are to attend peace talks next week in Geneva and to ensure the planned negotiations do not get derailed.
Russia, the main back of the Syrian government in the country's civil war, considers some key rebel groups to be terrorists and argues they should be excluded. The US and Russia met this week, trying to iron out differences, but they did not reach full accord.
Meanwhile, Syrian rebels are still insisting President Bashar al-Assad must step down before any transition can take place. Along with Turkey, the rebels are also interested in keeping the main Kurdish faction, the People's Protection Units (YPG), sidelined.
The YPG is the main US ally on the ground in pushing back the Islamic State in Syria while the Kurds in Iraq are also key players. Russia is also supportive of the Kurds' inclusion.
Biden started his meeting in Istanbul with Turkish Prime Minister Ahmet Davutoglu and was due to meet President Recep Tayyip Erdogan later.
"Fighting against [Islamic State] does not make them legitimate," Davutoglu said about the YPG. He was speaking with Turkish reporters en route back from Europe to Turkey, pro-government Sabah newspaper reported.
Both Turkey and Saudi Arabia hold influence among the Syrian opposition and back key Arab factions.
Kerry is also keen to reassure Gulf allies wary of involvement in the country by Iran, especially following the lifting of sanctions on Iran tied to the nuclear deal.
Saudi Arabia is worried about a stronger Iran and Tehran developing closer ties to the US. Iran, along with Russia, are the main supporters of al-Assad.
The Islamic State extremist group, which still holds a 90-kilometre stretch of land along the Syrian-Turkish border, is also expected to be discussed.
During his visit to Turkey, Biden was critical of a recent crackdown on academics calling for peace between the state and the Kurds. The vice president voiced support for more freedom of the press.